Skip to main content

Advertisement

SpringerLink
Log in

Emerging Applications of Hydroxypropyl Methylcellulose Acetate Succinate: Different Aspects in Drug Delivery and Its Commercial Potential

  • Review Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has multi-disciplinary applications spanning across the development of drug delivery systems, in 3D printing, and in tissue engineering, etc. HPMCAS helps in maintaining the drug in a super-saturated condition by inhibiting its precipitation, thereby increasing the rate and extent of dissolution in the aqueous media. HPMCAS has several distinctive characteristics, such as being amphiphilic in nature, having an ionization pH, and a succinyl and acetyl substitution ratio, all of which are beneficial while developing formulations. This review provides insights regarding the various types of formulations being developed using HPMCAS, including amorphous solid dispersion (ASD), amorphous nanoparticles, dry coating, and 3D printing, along with their applicability in drug delivery and biomedical fields. Furthermore, HPMCAS, compared with other carbohydrate polymers, shows several benefits in drug delivery, including proficiency in imparting stable ASD with a high dissolution rate, being easily processable, and enhancing bioavailability. The various commercially available formulations, regulatory considerations, and key patents containing the HPMCAS have been discussed in this review.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

API:

active pharmaceutical ingredient

ASD:

amorphous solid dispersion

BCS:

biopharmaceutical classification system

CMC:

carboxymethyl cellulose

CMCAB:

carboxy methylcellulose acetate butyrate

CAphth:

cellulose acetate phthalate

CA AdP:

cellulose acetate adipate

CA sub:

cellulose acetate suberate

CA seb:

cellulose acetate sebacate

CGMP:

current good manufacturing practice

CXB:

celecoxib

DCP:

dicalcium phosphate

EMA:

European Medical Agency

EU:

European Union

FDA-IID:

Food and Drug Administration-Inactive Ingredient Database

FDM:

fusion deposition modeling

GIT:

gastrointestinal tract

HPMCAS:

hydroxypropyl methylcellulose acetate succinate

HPMCP:

hydroxypropyl methylcellulose phthalate

HPMC:

hydroxypropyl methylcellulose

HLB:

hydrophilic-lipophilic balance

HPC:

hydroxypropyl cellulose

HME:

hot melt extrusion

JPE:

Japanese Pharmacopeia

MCC:

microcrystalline cellulose

NMR:

nuclear magnetic resonance

PVP:

polyvinyl pyrrolidone

PEG:

polyethylene glycol

PVA:

polyvinyl alcohol

S/A:

succinyl to acetyl

SDD:

spray-dried dispersion

SD:

solid dispersion

SSG:

sodium starch glycolate

Tg :

glass transition temperature

USP-NF:

United States Pharmacopeia-National Formulary

US-FDA:

United states-Food and Drug Administration

USA:

United States America

3D:

three dimensional

References

  1. Ford JL. Design and Evaluation of Hydroxypropyl Methylcellulose Matrix Tablets for Oral Controlled Release: A Historical Perspective. In: Timmins P, Pygall SR, Melia CD, editors. Hydrophilic Matrix Tablets for Oral Controlled Release, AAPS Advances in the Pharmaceutical Sciences Series. New York, NY: Springer; 2014. https://doi.org/10.1007/978-1-4939-1519-4_2.

  2. Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng. 2010;1:149–73. https://doi.org/10.1146/annurev-chembioeng-073009-100847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Moon RJ, Martini A, Nairn J, Simonsen J, Youngblood J. Cellulose nanomaterials review: structure, properties and nanocomposites. Chem Soc Rev. 2011;40(7):3941–94. https://doi.org/10.1039/C0CS00108B.

    Article  CAS  PubMed  Google Scholar 

  4. Nair LS, Laurencin CT. Polymers as biomaterials for tissue engineering and controlled drug delivery. Adv Biochem Eng Biotechnol. 2006;102:47–90. https://doi.org/10.1007/b137240.

    Article  CAS  PubMed  Google Scholar 

  5. Chavan RB, Rathi S, Jyothi VGSS, Shastri NR. Cellulose based polymers in development of amorphous solid dispersions. Asian J Pharm Sci. 2019;14(3):248–64. https://doi.org/10.1016/j.ajps.2018.09.003.

    Article  PubMed  Google Scholar 

  6. Sun S, Sun S, Cao X, Sun R. The role of pretreatment in improving the enzymatic hydrolysis of lignocellulosic materials. Bioresour Technol. 2016;199:49–58. Available from: https://www.sciencedirect.com/science/article/pii/S0960852415011670. Accessed 16 June 2022.

  7. French AD. Glucose, not cellobiose, is the repeating unit of cellulose and why that is important. Cellulose. 2017;24(11):4605–9. https://doi.org/10.1007/s10570-017-1450-3.

    Article  CAS  Google Scholar 

  8. Kamel S, Ali N, Jahangir K, Shah SM, El-Gendy AA. Pharmaceutical significance of cellulose: A review. Express Polym Lett. 2008;2:758–78. https://doi.org/10.3144/EXPRESSPOLYMLETT.2008.90.

    Article  CAS  Google Scholar 

  9. Arca HC, Mosquera-Giraldo LI, Bi V, Xu D, Taylor LS, Edgar KJ. Pharmaceutical applications of cellulose ethers and cellulose ether esters. Biomacromolecules. 2018;19(7):2351–76. https://doi.org/10.1021/acs.biomac.8b00517.

    Article  CAS  PubMed  Google Scholar 

  10. Chami Khazraji A, Robert S. Interaction Effects between Cellulose and Water in Nanocrystalline and Amorphous Regions: A Novel Approach Using Molecular Modeling. Jian SR, editor. J Nanomater. 2013;2013:409676. https://doi.org/10.1155/2013/409676.

  11. Vodak DT, Morgen M. Design and Development of HPMCAS-Based Spray-Dried Dispersions. In: Shah N, Sandhu H, Choi DS, Chokshi H, Malick AW, editors. Amorphous Solid Dispersions: Theory and Practice. New York, NY: Springer New York; 2014. p. 303–22. https://doi.org/10.1007/978-1-4939-1598-9_9.

    Chapter  Google Scholar 

  12. Bergenstråhle M, Wohlert J, Himmel ME, Brady JW. Simulation studies of the insolubility of cellulose. Carbohydr Res. 2010;345(14):2060–6. Available from: https://www.sciencedirect.com/science/article/pii/S0008621510002727. Accessed 17 June 2022.

  13. Lindman B, Medronho B, Alves L, Costa C, Edlund H, Norgren M. The relevance of structural features of cellulose and its interactions to dissolution, regeneration, gelation and plasticization phenomena. Phys Chem Chem Phys. 2017;19(35):23704–18. https://doi.org/10.1039/C7CP02409F.

    Article  CAS  PubMed  Google Scholar 

  14. Sharma P, Modi SR, Bansal AK. Co-processing as a tool to improve aqueous dispersibility of cellulose ethers. Drug Dev Ind Pharm. 2015;41(11):1745–58. https://doi.org/10.3109/03639045.2015.1058814.

    Article  CAS  PubMed  Google Scholar 

  15. Liu H, Taylor LS, Edgar KJ. The role of polymers in oral bioavailability enhancement; a review. Polymer. 2015;77:399–415. Available from: https://www.sciencedirect.com/science/article/pii/S0032386115302317. Accessed 15 July 2022.

  16. Hosny KM, Alkhalidi HM, Alharbi WS, Md S, Sindi AM, Ali SA, et al. Recent Trends in Assessment of Cellulose Derivatives in Designing Novel and Nanoparticulate-Based Drug Delivery Systems for Improvement of Oral Health. Polymers. 2022;14(1). https://doi.org/10.3390/polym14010092.

  17. Ciolacu DE, Nicu R, Ciolacu F. Cellulose-based hydrogels as sustained drug-delivery systems. Materials (Basel). 2020;13(22):1–37. https://doi.org/10.3390/ma13225270.

    Article  CAS  Google Scholar 

  18. Bhujbal SV, Mitra B, Jain U, Gong Y, Agrawal A, Karki S, et al. Pharmaceutical amorphous solid dispersion : a review of manufacturing strategies. Acta Pharm Sin B. 2021;11(8):2505–36. https://doi.org/10.1016/j.apsb.2021.05.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang M, Li W, You C, Wang Q, Zeng X, Chen M. Triboelectric nanogenerator based on 317L stainless steel and ethyl cellulose for biomedical applications. RSC Adv. 2017;7(11):6772–9. https://doi.org/10.1039/C6RA28252K.

    Article  CAS  Google Scholar 

  20. Nasatto PL, Pignon F, Silveira JLM, Duarte MER, Noseda MD, Rinaudo M. Methylcellulose, a cellulose derivative with original physical properties and extended applications. Polymers (Basel). 2015;7(5):777–803. Available from: https://www.mdpi.com/2073-4360/7/5/777.  Accessed 20 July 2022.

  21. Kozlowska J, Stachowiak N, Sionkowska A. Collagen/gelatin/hydroxyethyl cellulose composites containing microspheres based on collagen and gelatin: design and evaluation. polymers (Basel). 2018;10(4). Available from: https://www.mdpi.com/2073-4360/10/4/456. Accessed 20 July 2022.

  22. Jin C, Wu F, Hong Y, Shen L, Lin X, Zhao L, et al. Updates on applications of low-viscosity grade hydroxypropyl methylcellulose in coprocessing for improvement of physical properties of pharmaceutical powders. Carbohydr Polym. 2023;311(November 2022):120731. https://doi.org/10.1016/j.carbpol.2023.120731.

    Article  CAS  PubMed  Google Scholar 

  23. Edgar KJ, Buchanan CM, Debenham JS, Rundquist PA, Seiler BD, Shelton MC, et al. Advances in cellulose ester performance and application. Prog Polym Sci. 2001;26(9):1605–88. Available from: https://www.sciencedirect.com/science/article/pii/S0079670001000272. Accessed 9 Sept 2022.

  24. Fidale LC, Heinze T, El OA. Perichromism : a powerful tool for probing the properties of cellulose and its derivatives. Carbohydr Polym. 2013;93(1):129–34. https://doi.org/10.1016/j.carbpol.2012.06.061.

    Article  CAS  PubMed  Google Scholar 

  25. Chandel AKS, Shimizu A, Hasegawa K, Ito T. Advancement of biomaterial-based postoperative adhesion barriers. Macromol Biosci. 2021;21(3):1–34. https://doi.org/10.1002/mabi.202000395.

    Article  CAS  Google Scholar 

  26. Tanno F, Nishiyama Y, Kokubo H, Obara S. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions. Drug Dev Ind Pharm. 2004;30(1):9–17. https://doi.org/10.1081/DDC-120027506.

    Article  CAS  PubMed  Google Scholar 

  27. Heinze T, Koschella A. Carboxymethyl ethers of cellulose and starch – a review. Macromol Symp. 2005;223(1):13–40. https://doi.org/10.1002/masy.200550502.

    Article  CAS  Google Scholar 

  28. Liu J, Williams RO. Long-term stability of heat–humidity cured cellulose acetate phthalate coated beads. Eur J Pharm Biopharm. 2002;53(2):167–73. Available from: https://www.sciencedirect.com/science/article/pii/S093964110100234X. Accessed 21 July 2022.

  29. Lecomte F, Siepmann J, Walther M, MacRae RJ, Bodmeier R. Blends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns. J Control Release. 2003;89(3):457–71. Available from: https://www.sciencedirect.com/science/article/pii/S016836590300155X. Accessed 21 July 2022.

  30. Kar N, Liu H, Edgar KJ. Synthesis of cellulose adipate derivatives. Biomacromolecules. 2011;12(4):1106–15. https://doi.org/10.1021/bm101448f.

    Article  CAS  PubMed  Google Scholar 

  31. Liu H, Ilevbare GA, Cherniawski BP, Ritchie ET, Taylor LS, Edgar KJ. Synthesis and structure–property evaluation of cellulose ω-carboxyesters for amorphous solid dispersions. Carbohydr Polym. 2014;100:116–25. Available from: https://www.sciencedirect.com/science/article/pii/S0144861712011629. Accessed 11 Nov 2022.

  32. Obara S, Tanno FK, Sarode A. Properties and Applications of Hypromellose Acetate Succinate (HPMCAS) for Solubility Enhancement Using Melt Extrusion. In: Repka MA, Langley N, DiNunzio J, editors. Melt Extrusion: Materials, Technology and Drug Product Design. New York, NY: Springer New York; 2013. p. 107–21. https://doi.org/10.1007/978-1-4614-8432-5_4.

    Chapter  Google Scholar 

  33. Hoshi N, Yano H, Hirashima K, Kitagawa H, Fukuda Y. Toxicological studies of hydroxypropyl methylcellulose acetate succinate- acute toxicity in rats and rabbits, and subchronic and chronic toxicities in rats. J Toxicol Sci. 1970;10:147–85. Available from: http://www.mendeley.com/research/geology-volcanic-history-eruptive-style-yakedake-volcano-group-central-japan/. Accessed 3 Sept 2022.

  34. Shi SC, Su CC. Electrochemical behavior of hydroxypropyl methylcellulose acetate succinate as novel biopolymeric anticorrosion coating. Mater Chem Phys. 2020;248:122929. Available from: https://www.sciencedirect.com/science/article/pii/S0254058420303060. Accessed 3 Sept 2022.

  35. Butreddy A. Hydroxypropyl methylcellulose acetate succinate as an exceptional polymer for amorphous solid dispersion formulations: a review from bench to clinic. Eur J Pharm Biopharm. 2022;177(July):289–307. https://doi.org/10.1016/j.ejpb.2022.07.010.

    Article  CAS  PubMed  Google Scholar 

  36. Babu NR, Nagpal D, Ankola D, Awasthi R. Evolution of solid dispersion technology: solubility enhancement using hydroxypropyl methylcellulose acetate succinate: myth or reality? Assay Drug Dev Technol. 2022;20(4):149–63. https://doi.org/10.1089/adt.2022.016.

    Article  CAS  PubMed  Google Scholar 

  37. Curatolo W, Nightingale JA, Herbig SM. Utility of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) for Initiation and Maintenance of Drug Supersaturation in the GI Milieu. Pharm Res. 2009;26(6):1419–31. https://doi.org/10.1007/s11095-009-9852-z.

    Article  CAS  PubMed  Google Scholar 

  38. Brady J, Dürig T, Lee PI, Li JX. Chapter 7 - Polymer Properties and Characterization. In: Qiu Y, Chen Y, Zhang GGZ, Yu L, Mantri RV, editors. Developing Solid Oral Dosage Forms. 2nd ed. Boston: Academic Press; 2017. p. 181–223.

    Chapter  Google Scholar 

  39. Obara S, Kokubo H. Application of HPMC and HPMCAS to aqueous film coating of pharmaceutical dosage forms. In: Aqueous Polym Coatings Pharm Dos Forms. 3rd ed. CRC press; 2008. p. 279–322.

    Google Scholar 

  40. Klar F, Urbanetz NA. Solubility parameters of hypromellose acetate succinate and plasticization in dry coating procedures. Drug Dev Ind Pharm. 2016;42(10):1621–35. https://doi.org/10.3109/03639045.2016.1160106.

    Article  CAS  PubMed  Google Scholar 

  41. Friesen DT, Shanker R, Crew M, Smithey DT, Curatolo WJ, Nightingale JAS. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. Mol Pharm. 2008;5(6):1003–19. https://doi.org/10.1021/mp8000793.

    Article  CAS  PubMed  Google Scholar 

  42. Shah H, Jain AS, Laghate G, Prabhudesai D. Pharmaceutical excipients. Remington. 2021. https://doi.org/10.1016/b978-0-12-820007-0.00032-5.

    Article  Google Scholar 

  43. Idström A, Schantz S, Sundberg J, Chmelka BF, Gatenholm P, Nordstierna L. C NMR assignments of regenerated cellulose from solid-state 2D NMR spectroscopy. Carbohydr Polym. 2016;151:480–7. https://doi.org/10.1016/j.carbpol.2016.05.107.

    Article  CAS  PubMed  Google Scholar 

  44. Mašková E, Kubová K, Raimi-Abraham BT, Vllasaliu D, Vohlídalová E, Turánek J, et al. Hypromellose – a traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery. J Control Release. 2020;324(May):695–727. https://doi.org/10.1016/j.jconrel.2020.05.045.

    Article  CAS  PubMed  Google Scholar 

  45. Shinetsu. Shinetsu NF Hypermellose acetate succinate Shin-Etsu AQOAT; enteric coating agent. 2005. Available from: https://www.metolose.jp/en/pharmaceutical/aqoat.html. Accessed 3 Sept 2022.

  46. Carlson S, Nutrition A, Services H. Notice to US Food and Drug Administration of the Conclusion that the Intended Use of Shin-Etsu AQOAT® Hypromellose Acetate Succinate (HPMCAS) is Generally Recognized as Safe. 2020;(960). Available from: https://fda.report/media/148805/GRAS-Notice-GRN-960-Hypromellose-acetate-succinate.pdf. Accessed 15 March 2023.

  47. Verlag DA. USP 38 - NF 33 The United States Pharmacopeia and National Formulary 2015 Main edition plus Supplements 1 and 2. TA - TT. 1. Aufl. 2014.

  48. Japan K. oseisho. Yakumukyoku. K. K. S. o-ka Nihon Koteisho Kyokai., The Japanese pharmacopoeia 16. 16th edn. Tokyo: Society of Japanese Pharmacopoeia, Distributed by Yakuji Nippo (2016).

  49. Kim SJ, Lee HK, Na YG, Bang KH, Lee HJ, Wang M, et al. A novel composition of ticagrelor by solid dispersion technique for increasing solubility and intestinal permeability. Int J Pharm. 2019;555(September 2018):11–8. https://doi.org/10.1016/j.ijpharm.2018.11.038.

    Article  CAS  PubMed  Google Scholar 

  50. Wang Y, Fang Y, Zhou F, Liang Q, Deng Y. The amorphous quercetin/ hydroxypropylmethylcellulose acetate succinate solid dispersions prepared by co-precipitation method to enhance quercetin dissolution. J Pharm Sci. 2021;110(9):3230–7. Available from: https://www.sciencedirect.com/science/article/pii/S0022354921002483. Accessed 25 Sept 2022.

  51. Ueda K, Higashi K, Yamamoto K, Moribe K. The effect of HPMCAS functional groups on drug crystallization from the supersaturated state and dissolution improvement. Int J Pharm. 2014;464(1):205–13. Available from: https://www.sciencedirect.com/science/article/pii/S0378517314000155. Accessed 25 Sept 2022.

  52. AquaSolve Hydroxypropyl methyl cellulose acetate succinate: Physical and chemical properties handbook. 2021;1–15. Available from: https://www.ashland.com/file_source/Ashland/Industries/Pharmaceutical/Links/PC-12624.6_AquaSolve_HPMCAS_Physical_Chemical_Properties.pdf. Accessed 3 July 2022.

  53. AFFINISOL TM HPMCAS for Spray-Dried Dispersion (SDD) Solving the Insoluble. 2021;1–10. Available from: https://www.scribd.com/document/526635758/AFFINISOL-Technical-Brochure-for-web-0217. Accessed 3 July 2022.

  54. Carpentier P. The three dimensional solubility parameter and solvent diffusion coefficient their importance in surface coating formulation. 1967;1–104. Available from: https://hansen-solubility.com/contents/HSP1967-OCR.pdf. Accessed 5 July 2022.

  55. Jelić D. Thermal Stability of Amorphous Solid Dispersions. Molecules. 2021;26(1):238. https://doi.org/10.3390/molecules26010238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Babu NR, Nagpal D, Ankola D, Awasthi R. Evolution of solid dispersion technology: solubility enhancement using hydroxypropyl methylcellulose acetate succinate: myth or reality? Assay Drug Dev Technol. 2022;20(4):149–63. https://doi.org/10.1089/adt.2022.016.

    Article  CAS  PubMed  Google Scholar 

  57. Hoshi N, Ueno K, Yano H, Hirashima K, Kitagawa H. General pharmacological studies of hydroxypropylmethylcellulose acetate succinate in experimental animals. J Toxicol Sci. 1985;10(Suppl 2):129–46. https://doi.org/10.2131/jts.10.supplementii_129.

    Article  CAS  PubMed  Google Scholar 

  58. Krishnaiah YSR. Pharmaceutical Technologies for Enhancing Oral Bioavailability of Poorly Soluble Drugs. J Bioequivalence Bioaviliability. 2010;2(2):28–36. https://doi.org/10.4172/jbb.1000027.

    Article  CAS  Google Scholar 

  59. Göke K, Lorenz T, Repanas A, Schneider F, Steiner D, Baumann K, et al. Novel strategies for the formulation and processing of poorly water-soluble drugs. Eur J Pharm Biopharm. 2018;126:40–56. Available from: https://www.sciencedirect.com/science/article/pii/S093964111730156X. Accessed 26 Sept 2022.

  60. Vemula VR, Lagishetty V, Lingala S. Solubility Enhancement Techniques. Int J Pharm Sci Rev Res. 2010;5(1):41–51.

    CAS  Google Scholar 

  61. Savjani KT, Gajjar AK, Savjani JK. Drug Solubility : Importance and Enhancement Techniques. ISRN Pharm. 2012;1–10. https://doi.org/10.5402/2012/195727.

  62. Winslow CJ, Nichols BLB, Novo DC, Mosquera-Giraldo LI, Taylor LS, Edgar KJ, et al. Cellulose-based amorphous solid dispersions enhance rifapentine delivery characteristics in vitro. Carbohydr Polym. 2018;182:149–58. https://doi.org/10.1016/j.carbpol.2017.11.024.

    Article  CAS  PubMed  Google Scholar 

  63. Shah N, Iyer RM, Mair HJ, Choi D, Tian H, Diodone R, et al. Improved Human Bioavailability of Vemurafenib, a Practically Insoluble Drug, Using an Amorphous Polymer-Stabilized Solid Dispersion Prepared by a Solvent-Controlled Coprecipitation Process. J Pharm Sci. 2013;102(3):967–81. https://doi.org/10.1002/jps.23425.

    Article  CAS  PubMed  Google Scholar 

  64. de Oliveira HP, Albuquerque JJF, Nogueiras C, Rieumont J. Physical chemistry behavior of enteric polymer in drug release systems. Int J Pharm. 2009;366(1):185–9. Available from: https://www.sciencedirect.com/science/article/pii/S0378517308006042. Accessed 20 Dec 2022.

  65. Missaghi S, Young C, Fegely K, Rajabi-siahboomi AR. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies. Drug Dev Ind Pharm. 2010;36(2):180–9. https://doi.org/10.3109/03639040903468811.

    Article  CAS  PubMed  Google Scholar 

  66. Liu J, Li Y, Ao W, Xiao Y, Bai M, Li S. Preparation and characterization of aprepitant solid dispersion with HPMCAS-LF. ACS Omega. 2022;7(44):39907–12. https://doi.org/10.1021/acsomega.2c04021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Stroyer A, McGinity JW, Leopold CS. Solid state interactions between the proton pump inhibitor omeprazole and various enteric coating polymers. J Pharm Sci. 2006;95(6):1342–53. https://doi.org/10.1002/jps.20450.

    Article  CAS  PubMed  Google Scholar 

  68. Qin Y, Xiao C, Li X, Huang J, Si L, Sun M. Enteric Polymer-Based Amorphous Solid Dispersions Enhance Oral Absorption of the Weakly Basic Drug Nintedanib via Stabilization of Supersaturation. Pharmaceutics. 2022;14(9):1830. https://doi.org/10.3390/pharmaceutics14091830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fu M, Blechar JA, Sauer A, Al-Gousous J, Langguth P. In vitro evaluation of enteric-coated HPMC capsules—effect of formulation factors on product performance. Pharmaceutics. 2020;12(8):1–17. https://doi.org/10.3390/pharmaceutics12080696.

    Article  CAS  Google Scholar 

  70. Siepmann F, Siepmann J, Walther M, MacRae R, Bodmeier R. Aqueous HPMCAS coatings: effects of formulation and processing parameters on drug release and mass transport mechanisms. Eur J Pharm Biopharm. 2006;63(3):262–9. https://doi.org/10.1016/j.ejpb.2005.12.009.

    Article  CAS  PubMed  Google Scholar 

  71. Riedel A, Leopold CS. Degradation of Omeprazole Induced by Enteric Polymer Solutions and Aqueous Dispersions: HPLC Investigations. Drug Dev Ind Pharm. 2005;31(2):151–60. https://doi.org/10.1081/DDC-200047787.

    Article  CAS  PubMed  Google Scholar 

  72. Story MJ. Enteric-coated pellets: Theoretical analysis of effect of dispersion in the stomach on blood level profiles. J Pharm Sci. 1977;66(10):1495–6. https://doi.org/10.1002/jps.2600661042.

    Article  CAS  PubMed  Google Scholar 

  73. Shravani D, Lakshmi PK, Balasubramaniam J. Preparation and optimization of various parameters of enteric coated pellets using the Taguchi L9 orthogonal array design and their characterization. Acta Pharm Sin B. 2011;1(1):56–63. https://doi.org/10.1016/j.apsb.2011.04.005.

    Article  CAS  Google Scholar 

  74. Pinto JMO, Leão AF, Riekes MK, França MT, Stulzer HK. HPMCAS as an effective precipitation inhibitor in amorphous solid dispersions of the poorly soluble drug candesartan cilexetil. Carbohydr Polym. 2018;184:199–206. Available from: https://www.sciencedirect.com/science/article/pii/S0144861717314583. Accessed 17 Nov 2022.

  75. Nguyen HT, Van Duong T, Taylor LS. Impact of Gastric pH Variations on the Release of Amorphous Solid Dispersion Formulations Containing a Weakly Basic Drug and Enteric Polymers. Mol Pharm. 2023;20(3):1681–95. https://doi.org/10.1021/acs.molpharmaceut.2c00895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Gan Y, Baak JPA, Chen T, Ye H, Liao W, Lv H, et al. Supersaturation and Precipitation Applicated in Drug Delivery Systems: Development Strategies and Evaluation Approaches. Molecules. 2023;28(5):2212. https://doi.org/10.3390/molecules28052212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Xie T, Taylor LS. Dissolution performance of high drug loading celecoxib amorphous solid dispersions formulated with polymer combinations. Pharm Res. 2016;33(3):739–50. https://doi.org/10.1007/s11095-015-1823-y.

    Article  CAS  PubMed  Google Scholar 

  78. Konno H, Taylor LS. Ability of different polymers to inhibit the crystallization of amorphous felodipine in the presence of moisture. Pharm Res. 2008;25(4):969–78. https://doi.org/10.1007/s11095-007-9331-3.

    Article  CAS  PubMed  Google Scholar 

  79. Ueda K, Higashi K, Yamamoto K, Moribe K. Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements. Mol Pharm. 2013;10(10):3801–11. https://doi.org/10.1021/mp400278j.

    Article  CAS  PubMed  Google Scholar 

  80. Chen H, Pui Y, Liu C, Chen Z, Su CC, Hageman M, et al. Moisture-induced amorphous phase separation of amorphous solid dispersions: molecular mechanism, microstructure, and its impact on dissolution performance. J Pharm Sci. 2018;107(1):317–26. https://doi.org/10.1016/j.xphs.2017.10.028.

    Article  CAS  PubMed  Google Scholar 

  81. Yu D, Li J, Wang H, Pan H, Li T, Bu T, et al. Role of polymers in the physical and chemical stability of amorphous solid dispersion: a case study of carbamazepine. Eur J Pharm Sci. 2022;169:106086. https://doi.org/10.1016/j.ejps.2021.106086.

    Article  CAS  PubMed  Google Scholar 

  82. Rumondor ACF, Taylor LS. Effect of polymer hygroscopicity on the phase behavior of amorphous solid dispersions in the presence of moisture. Mol Pharm. 2010;7(2):477–90. https://doi.org/10.1021/mp9002283.

    Article  CAS  PubMed  Google Scholar 

  83. Rumondor ACF, Stanford LA, Taylor LS. Effects of polymer type and storage relative humidity on the kinetics of felodipine crystallization from amorphous solid dispersions. Pharm Res. 2009;26(12):2599–606. https://doi.org/10.1007/s11095-009-9974-3.

    Article  CAS  PubMed  Google Scholar 

  84. Cunningham CR, Fegely KA. One-step aqueous enteric coating systems: scale-up evaluation. Pharmaceutical technology. 2001;25(11):36.

  85. Luo Y, Zhu J, Ma Y, Zhang H. Dry coating, a novel coating technology for solid pharmaceutical dosage forms. Int J Pharm. 2008;358(1):16–22. Available from: https://www.sciencedirect.com/science/article/pii/S0378517308002330. Accessed 6 Dec 2022.

  86. Ivanova E, Teunou E, Poncelet D. Encapsulation of water sensitive products: Effectiveness and assessment of fluid bed dry coating. J Food Eng. 2005;71(2):223–30. https://doi.org/10.1016/j.jfoodeng.2004.10.037.

    Article  Google Scholar 

  87. Obara S, Maruyama N, Nishiyama Y, Kokubo H. Dry coating: an innovative enteric coating method using a cellulose derivative. Eur J Pharm Biopharm. 1999;47(1):51–9. Available from: https://www.sciencedirect.com/science/article/pii/S0939641198000873. Accessed 6 Dec 2022.

  88. Kablitz C. Caroline Kablitz, Dry coating – a characterization and optimization of an innovative coating technology. 2007;49:0–8. Available from: https://cuvillier.de/uploads/preview/public_file/3682/9783867273220.pdf. Accessed 6 Dec 2022.

  89. Cerea M, Foppoli A, Maroni A, Palugan L, Zema L, Sangalli ME. Dry Coating of Soft Gelatin Capsules with HPMCAS. Drug Dev Ind Pharm. 2008;34(11):1196–200. https://doi.org/10.1080/03639040801974360.

    Article  CAS  PubMed  Google Scholar 

  90. Van den Mooter G. The use of amorphous solid dispersions: a formulation strategy to overcome poor solubility and dissolution rate. Drug Discov Today Technol. 2012;9(2):e79–85. Available from: https://www.sciencedirect.com/science/article/pii/S1740674911000205. Accessed on July 3, 2022.

  91. Monschke M, Wagner KG. Impact of HPMCAS on the dissolution performance of polyvinyl alcohol celecoxib amorphous solid dispersions. Pharmaceutics. 2020;12(6):541. https://doi.org/10.3390/pharmaceutics12060541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Choudhari M, Donthi M, Damle S, Singhvi G, Saha R, Dubey S. Implementation of quality by design approach for optimization of RP-HPLC method for quantification of abiraterone acetate in solid dispersion in forced degradation studies. Curr Chromatogr 2022;9(1). https://doi.org/10.2174/2213240609666221110090339.

  93. Damle S, Choudhari M, Singhvi G, Saha RN, Dubey SK. Development and validation of reverse-phase high-performance liquid chromatography method for estimation of itraconazole through hydroxypropyl methylcellulose acetate succinate based polymeric films using quality by design principles. Sep Sci PLUS. 2021;4(11–12):388–400. https://doi.org/10.1002/sscp.202100037.

    Article  CAS  Google Scholar 

  94. Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci. 1971;60(9):1281–302. Available from: https://www.sciencedirect.com/science/article/pii/S0022354915380850. Accessed on July 3, 2022.

  95. Vaka S., Bommana M., Desai D., Djordjevic J., Phuapradit W. SN. Excipients for amorphous solid dispersions, Advances in Delivery Science and Technology. Springer, New York, NY. 2014; https://doi.org/10.1007/978-1-4939-1598-9_4.

  96. Dahan A, Beig A, Ioffe-Dahan V, Agbaria R, Miller JM. The Twofold Advantage of the Amorphous Form as an Oral Drug Delivery Practice for Lipophilic Compounds: Increased Apparent Solubility and Drug Flux Through the Intestinal Membrane. AAPS J. 2013;15(2):347–53. https://doi.org/10.1208/s12248-012-9445-3.

    Article  CAS  PubMed  Google Scholar 

  97. Yang R, Mann AKP, Van Duong T, Ormes JD, Okoh GA, Hermans A, et al. Drug release and nanodroplet formation from amorphous solid dispersions: insight into the roles of drug physicochemical properties and polymer selection. Mol Pharm. 2021;18(5):2066–81. https://doi.org/10.1021/acs.molpharmaceut.1c00055.

    Article  CAS  PubMed  Google Scholar 

  98. Gutzow I. SJ. General approaches in the description of the structure of glasses. In: The Vitreous State. Springer, Berlin, Heidelberge. 1995; https://doi.org/10.1007/978-3-662-03187-2_4.

  99. Baghel S, Cathcart H, O’Reilly NJ. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci. 2016;105(9):2527–44. Available from: https://www.sciencedirect.com/science/article/pii/S002235491500009X. Accessed 7 Dec 2022.

  100. Vasconcelos T, Marques S, das Neves J, Sarmento B. Amorphous solid dispersions: rational selection of a manufacturing process. Adv Drug Deliv Rev. 2016;100:85–101. Available from: https://www.sciencedirect.com/science/article/pii/S0169409X16300291. Accessed 7 Dec 2022.

  101. Rampal A, Singh M, Mahajan S, Bedi N. Formulation and characterization of HPMC and HPMCAS based solid dispersions of fenofibrate: a comparative study. Int J Appl Pharm. 2019;11(4):41–8. https://doi.org/10.22159/ijap.2019v11i4.32592.

    Article  CAS  Google Scholar 

  102. Jung J, Shin KI, Lee M, Song M, Kwon S. Enhanced solubility through particle size control, modification of crystal behavior, and crystalline form changes in solid dispersion of nifedipine. Biotechnol Bioprocess Eng. 2021;110:105–10. https://doi.org/10.1007/s12257-021-0147-5.

    Article  CAS  Google Scholar 

  103. Solanki NG, Lam K, Gumaste SG, Shah A V, Serajuddin ATM. Effects of surfactants on itraconazole-HPMCAS solid dispersion prepared by hot-melt extrusion I : miscibility and drug release. J Pharm Sci. 2018;1–13. https://doi.org/10.1016/j.xphs.2018.10.058.

  104. Nakamichi K, Nakano T, Izumi S, Yasuura H, Kawashima Y. The preparation of enteric solid dispersions with hydroxypropylmethylcellulose acetate succinate using a twin-screw extruder. J Drug Deliv Sci Technol. 2004;14:193–8. https://doi.org/10.1016/S1773-2247(04)50100-4.

    Article  CAS  Google Scholar 

  105. Deng W, Majumdar S, Singh A, Shah S, Mohammed NN, Jo S, et al. Stabilization of fenofibrate in low molecular weight hydroxypropylcellulose matrices produced by hot-melt extrusion. Drug Dev Ind Pharm. 2013;39(2):290–8. https://doi.org/10.3109/03639045.2012.679280.

    Article  CAS  PubMed  Google Scholar 

  106. Wu C, McGinity JW. Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit® RS PO hot-melt extrudates. Eur J Pharm Biopharm. 2003;56(1):95–100. Available from: https://www.sciencedirect.com/science/article/pii/S0939641103000353. Accessed 10 Dec 2022.

  107. Ashour EA, Kulkarni V, Almutairy B, Park JB, Shah SP, Majumdar S, et al. Influence of pressurized carbon dioxide on ketoprofen-incorporated hot-melt extruded low molecular weight hydroxypropylcellulose. Drug Dev Ind Pharm. 2016;42(1):123–30. https://doi.org/10.3109/03639045.2015.1035282.

    Article  CAS  Google Scholar 

  108. Verreck G, Decorte A, Li H, Tomasko D, Arien A, Peeters J, et al. The effect of pressurized carbon dioxide as a plasticizer and foaming agent on the hot melt extrusion process and extrudate properties of pharmaceutical polymers. J Supercrit Fluids. 2006;38(3):383–91. https://doi.org/10.1016/j.ejps.2005.07.006.

    Article  CAS  Google Scholar 

  109. Almutairi M. Feasibility of AquasolveTM HPMC-AS Lg via Hot-melt Extrusion: Effect of Pressurized CO2 on Physico-mechanical Properties, Electronic Theses and Dissertations. 2018, 1338. Available from: https://egrove.olemiss.edu/etd/1338. Accessed 15 Dec 2022.

  110. Iyer R, Hegde S, Zhang YE, Dinunzio J, Singhal D, Malick A, et al. The Impact of Hot Melt Extrusion and Spray Drying on Mechanical Properties and Tableting Indices of Materials Used in Pharmaceutical Development. J Pharm Sci. 2013;102(10):3604–13. https://doi.org/10.1002/jps.23661.

    Article  CAS  PubMed  Google Scholar 

  111. Zhang W, Noland R, Chin S, Petkovic M, Zuniga R, Santarra B, et al. Impact of polymer type, ASD loading and polymer-drug ratio on ASD tablet disintegration and drug release. Int J Pharm. 2021;592:120087. https://doi.org/10.1016/j.ijpharm.2020.120087.

    Article  CAS  PubMed  Google Scholar 

  112. Sauer A, Warashina S, Mishra SM, Lesser I, Kirchhöfer K. Downstream processing of spray-dried ASD with hypromellose acetate succinate – Roller compaction and subsequent compression into high ASD load tablets. Int J Pharm X. 2021;3. https://doi.org/10.1016/j.ijpx.2021.100099.

  113. Jog R, Burgess DJ. Pharmaceutical amorphous nanoparticles. J Pharm Sci. 2016;1–27. https://doi.org/10.1016/j.xphs.2016.09.014.

  114. Feng J, Zhang Y, McManus SA, Ristroph KD, Lu HD, Gong K, et al. Rapid Recovery of Clofazimine-Loaded Nanoparticles with Long-Term Storage Stability as Anti-Cryptosporidium Therapy. ACS Appl Nano Mater. 2018;1(5):2184–94. https://doi.org/10.1021/acsanm.8b00234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Feng J, Zhang Y, McManus SA, Qian R, Ristroph KD, Ramachandruni H, et al. Amorphous nanoparticles by self-assembly: processing for controlled release of hydrophobic molecules. Soft Matter. 2019;15(11):2400–10. https://doi.org/10.1039/C8SM02418A.

    Article  CAS  PubMed  Google Scholar 

  116. Ristroph KD, Feng J, Mcmanus SA, Zhang Y, Gong K, Ramachandruni H, et al. Spray drying OZ439 nanoparticles to form stable, water‑dispersible powders for oral malaria therapy. J Transl Med. 2019;1–12. https://doi.org/10.1186/s12967-019-1849-8.

  117. Giri BR, Poudel S, Kim DW. Cellulose and its derivatives for application in 3D printing of pharmaceuticals. J Pharm Investig. 2021;51(1). https://doi.org/10.1007/s40005-020-00498-5.

  118. Cheng Y, Shi X, Jiang X, Wang X, Qin H. Printability of a cellulose derivative for extrusion-based 3D printing: the application on a biodegradable support material. Front Mater. 2020;7:3–8. https://doi.org/10.3389/fmats.2020.00086.

    Article  Google Scholar 

  119. Oladeji S, Mohylyuk V, Jones DS, Andrews GP. 3D printing of pharmaceutical oral solid dosage forms by fused deposition: the enhancement of printability using plasticised HPMCAS. Int J Pharm. 2022;616(October 2021):121553. https://doi.org/10.1016/j.ijpharm.2022.121553.

    Article  CAS  PubMed  Google Scholar 

  120. Polamaplly P, Cheng Y, Shi X, Manikandan K, Kremer GE, Qin H. 3D printing and characterization of hydroxypropyl methylcellulose and methylcellulose for biodegradable support structures. Procedia Manuf. 2019;34:552–9. https://doi.org/10.1016/j.promfg.2019.06.219.

    Article  Google Scholar 

  121. Bandari S, Nyavanandi D, Dumpa N, Repka MA. Coupling hot melt extrusion and fused deposition modeling: critical properties for successful performance. Adv Drug Deliv Rev. 2021;172:52–63. Available from: https://www.sciencedirect.com/science/article/pii/S0169409X21000405. Accessed 10 Dec 2022.

  122. Tabriz AG, Scoutaris N, Gong Y, Hui HW, Kumar S, Douroumis D. Investigation on hot melt extrusion and prediction on 3D printability of pharmaceutical grade polymers. Int J Pharm. 2021;604(April):120755. https://doi.org/10.1016/j.ijpharm.2021.120755.

    Article  CAS  PubMed  Google Scholar 

  123. Scoutaris N, Ross SA, Douroumis D. 3D Printed “Starmix” drug loaded dosage forms for paediatric applications. Pharm Res. 2018;35(2):1–11. https://doi.org/10.1007/s11095-018-2454-x.

    Article  CAS  Google Scholar 

  124. Goyanes A, Fina F, Martorana A, Sedough D, Gaisford S, Basit AW. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. Int J Pharm. 2017;527(1–2):21–30. https://doi.org/10.1016/j.ijpharm.2017.05.021.

    Article  CAS  PubMed  Google Scholar 

  125. Kaushal AM, Gupta PBA. Amorphous drug delivery systems: molecular aspects, design, and performance. Crit Rev Ther Drug Carr Syst. 2004;21(3):133–93. https://doi.org/10.1615/critrevtherdrugcarriersyst.v21.i3.10.

    Article  CAS  Google Scholar 

  126. Ghosh I, Snyder J, Vippagunta R, Alvine M, Vakil R, Tong WQ (Tony), et al. Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder. Int J Pharm. 2011;419(1):12–9. Available from: https://www.sciencedirect.com/science/article/pii/S0378517311005254. Accessed 6 Dec 2022.

  127. Raina SA, Van Eerdenbrugh B, Alonzo DE, Mo H, Zhang GGZ, Gao Y, et al. Trends in the precipitation and crystallization behavior of supersaturated aqueous solutions of poorly water-soluble drugs assessed using synchrotron radiation. J Pharm Sci. 2015;104(6):1981–92. https://doi.org/10.1002/jps.24423.

    Article  CAS  PubMed  Google Scholar 

  128. Fang Y, Wang G, Zhang R, Liu Z, Liu Z, Wu X, et al. Eudragit L/HPMCAS Blend Enteric-Coated Lansoprazole Pellets: Enhanced Drug Stability and Oral Bioavailability. AAPS PharmSciTech. 2014;15(3):513–21. https://doi.org/10.1208/s12249-013-0035-1.

  129. Seddiqi H, Oliaei E, Honarkar H, Jin J. Cellulose and its derivatives : towards biomedical applications. Vol. 28, Cellulose. Springer Netherlands; 2021. 1893–1931. https://doi.org/10.1007/s10570-020-03674-w.

  130. Ohta S, Mitsuhashi K, Chandel AKS, Qi P, Nakamura N, Nakamichi A, et al. Silver-loaded carboxymethyl cellulose nonwoven sheet with controlled counterions for infected wound healing. Carbohydr Polym. 2022;286:119289. Available from: https://www.sciencedirect.com/science/article/pii/S014486172200193X. Accessed 24 March 2023.

  131. Farzamfar S, Naseri-Nosar M, Vaez A, Esmaeilpour F, Ehterami A, Sahrapeyma H, et al. Neural tissue regeneration by a gabapentin-loaded cellulose acetate/gelatin wet-electrospun scaffold. Cellulose. 2018;25(2):1229–38. https://doi.org/10.1007/s10570-017-1632-z.

    Article  CAS  Google Scholar 

  132. Zulkifli FH, Hussain FSJ, Zeyohannes SS, Rasad MSBA, Yusuff MM. A facile synthesis method of hydroxyethyl cellulose-silver nanoparticle scaffolds for skin tissue engineering applications. Mater Sci Eng C. 2017;79:151–60. Available from: https://www.sciencedirect.com/science/article/pii/S092849311630950X. Accessed 24 March 2023.

  133. Wutticharoenmongkol P, Hannirojram P, Nuthong P. Gallic acid-loaded electrospun cellulose acetate nanofibers as potential wound dressing materials. Polym Adv Technol. 2019;30(4):1135–47. https://doi.org/10.1002/pat.4547.

    Article  CAS  Google Scholar 

  134. Henschen J, Illergård J, Larsson PA, Ek M, Wågberg L. Contact-active antibacterial aerogels from cellulose nanofibrils. Colloids Surfaces B Biointerfaces. 2016;146:415–22. Available from: https://www.sciencedirect.com/science/article/pii/S0927776516304611. Accessed 24 March 2023.

  135. Tipduangta P, Belton P, Fábián L, Wang LY, Tang H, Eddleston M, et al. Electrospun polymer blend nanofibers for tunable drug delivery: the role of transformative phase separation on controlling the release rate. Mol Pharm. 2016;13(1):25–39. https://doi.org/10.1021/acs.molpharmaceut.5b00359.

    Article  CAS  PubMed  Google Scholar 

  136. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20. https://doi.org/10.1023/A:1016212804288.

    Article  CAS  PubMed  Google Scholar 

  137. Brouwers J, Brewster ME, Augustijns P. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J Pharm Sci. 2009;98(8):2549–72. Available from: https://www.sciencedirect.com/science/article/pii/S0022354916330271. Accessed 5 Aug 2023.

  138. Bevernage J, Brouwers J, Brewster ME, Augustijns P. Evaluation of gastrointestinal drug supersaturation and precipitation: strategies and issues. Int J Pharm. 2013;453(1):25–35. Available from: https://www.sciencedirect.com/science/article/pii/S0378517312010332. Accessed 4 Jan 2023.

  139. Gan Y, Baak JPA, Chen T, Ye H, Liao W, Lv H, et al. Supersaturation and Precipitation Applicated in Drug Delivery Systems: Development Strategies and Evaluation Approaches. Molecules. 2023;28(5):2212. https://doi.org/10.3390/molecules28052212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Mitra A, Fadda HM. Effect of surfactants, gastric emptying, and dosage form on supersaturation of dipyridamole in an in vitro model simulating the stomach and duodenum. Mol Pharm. 2014;11(8):2835–44. https://doi.org/10.1021/mp500196f.

    Article  CAS  PubMed  Google Scholar 

  141. Plum J, Bavnhøj C, Palmelund H, Pérez-Alós L, Müllertz A, Rades T. Comparison of induction methods for supersaturation: pH shift versus solvent shift. Int J Pharm. 2020;573:118862. https://doi.org/10.1016/j.ijpharm.2019.118862.

    Article  CAS  PubMed  Google Scholar 

  142. Warren DB, Benameur H, Porter CJH, Pouton CW. Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: a mechanistic basis for utility. J Drug Target. 2010;18(10):704–31. https://doi.org/10.3109/1061186X.2010.525652.

    Article  CAS  PubMed  Google Scholar 

  143. Ilevbare GA, Liu H, Edgar KJ, Taylor LS. Maintaining supersaturation in aqueous drug solutions: impact of different polymers on induction times. Cryst Growth Des. 2013;13(2):740–51. https://doi.org/10.1021/cg301447d.

    Article  CAS  Google Scholar 

  144. Teja SB, Patil SP, Shete G, Patel S, Bansal AK. Drug-excipient behavior in polymeric amorphous solid dispersions. J Excipients Food Chem. 2014;4(3):70–94.

    Google Scholar 

  145. Karimi-Jafari M, Padrela L, Walker GM, Croker DM. Creating cocrystals: a review of pharmaceutical cocrystal preparation routes and applications. Cryst Growth Des. 2018;18(10):6370–87. https://doi.org/10.1021/acs.cgd.8b00933.

    Article  CAS  Google Scholar 

  146. Bavishi DD, Borkhataria CH. Spring and parachute: how cocrystals enhance solubility. Prog Cryst Growth Charact Mater. 2016;62(3):1–8. https://doi.org/10.1016/j.pcrysgrow.2016.07.001.

    Article  CAS  Google Scholar 

  147. Shi Q, Chen H, Wang Y, Wang R, Xu J, Zhang C. Amorphous Solid Dispersions: Role of the Polymer and Its Importance in Physical Stability and In Vitro Performance. Pharmaceutics. 2022;14(8):1747. https://doi.org/10.3390/pharmaceutics14081747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Vo CLN, Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm. 2013;85(3, Part B):799–813. Available from: https://www.sciencedirect.com/science/article/pii/S0939641113003007. Accessed 3 July 2022.

  149. Marques S, Sarmento B. Amorphous solid dispersions: rational selection of a manufacturing process. Adv Drug Deliv Rev journa. 2016. https://doi.org/10.1016/j.addr.2016.01.012.

  150. He YAN, Ho C. Amorphous solid dispersions : utilization and challenges in drug. J Pharm Sci. 2015;104(10):3237–58. https://doi.org/10.1002/jps.24541.

    Article  CAS  PubMed  Google Scholar 

  151. USFDA. ERLEADA is indicated for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) non-metastatic castration-resistant prostate cancer (nmCRP). 2019.

  152. Jermain S V, Brough C, Williams RO. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery – an update. Int J Pharm. 2018;535(1):379–92. Available from: https://www.sciencedirect.com/science/article/pii/S0378517317310311. Accessed 3 July 2022.

  153. Jermain AS V, Brough C, Williams RO. SC. Int J Pharm. 2017; https://doi.org/10.1016/j.ijpharm.2017.10.051.

  154. Pandi P, Bulusu R, Kommineni N, Khan W, Singh M. Amorphous solid dispersions: an update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. Int J Pharm. 2020;586:1–28. https://doi.org/10.1016/j.ijpharm.2020.119560.

    Article  CAS  Google Scholar 

  155. Tran P, Pyo Y-C, Kim D-H, Lee S-E, Kim J-K, Park J-S. Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs. Pharmaceutics. 2019;11(3):132. https://doi.org/10.3390/pharmaceutics11030132.

  156. Food and Drug Administration. US- full prescribing information for IDHIFA. highlights include all the information needed to use IDHIFA safely and effectively. Food drug Adm. 2017; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf. Accessed 23 Dec 2022.

  157. Food and drug Administration. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use SYMDEKO safely and effectively. 2018;(14):1–15. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210491lbl.pdf. Accessed 3 Jan 2023.

  158. Andrson NR. Duloxetine Enteric Pellets. US patent application US005508276A. 1996.

  159. Fang LY, Wan J, Harris D. Oral pharmaceutical compositions in a solid dispersion comprising preferably posaconazole and HPMCAS. 2011;1(19):1–10. Available from: https://patents.google.com/patent/US20110034478A1/en. Accessed 22 Dec 2022.

  160. Cade DN, Straub H. Aqueous dispersions of hydroxypropyl methylcellulose acetate succinate (hpmcas). EPO publication number EP2844296A1. 2013.

  161. Kusaki F. Composition for Hot melt extrusion and method for producing hot melt extrusion product using same. US patent application US 2014/0357681 A1. Vol. 1. 2014.

  162. Maruyama, N., Warashina, S., Kusaki, F., Obara, S. and Kikuchi K. Hypromellose acetate succinate for use as hot-melt extrusion carrier, hot-melt extrusion composition, and method for producing hot-melt extrudate. US patent application 14/453,935. Vol. 1. 2015. p. 1–14.

  163. Friesen DT, Caldwell WB, Vodak DT, Dobry E. Hydroxypropyl methyl cellulose acetate succinate with enhanced acetate and succinate substitution. US patent application US009040033B2. 2015; 2.

  164. Bang SH, Shin JH, Son JR, Park KY, Chun JH, Jeong JS, Lee SY. LFCCL. Method for preparing hydroxypropyl methylcellulose acetate succinate (HPMCAS) grains having controlled grain size distribution, and HPMCAS powder. EPO publication number EP3091036A1. 2020.

  165. Lehmann F. Composition comprising vemurafenib and HPMC-AS. EPO publication number EP3072529B1. 2017;1–19.

  166. Allen M, Sandhu HK, Orange W, Shah NH, Zhang Y e. Pharmaceutical composition with improved bioaviliability. US patent application US2017/0000764 A1. 2017;1(19).

  167. Morgan MM. Formulation to achieve rapid dissolution of drug from spray dried dispersion in capsules. WIPO publication number WO2016198983A1. 2016.

  168. Perrine.P. New oral formulation of Belinostat. WIPO publication number WO2019002614A1. 2019.

  169. Verreck G. Anticancer composition. EPO Publication number EP003226843B1. Vol. 1. 2021. p. 1–26.

  170. Zhou X. Solid dispersion and preparation method therefor. US patent application US20220233449A1. 2022.

  171. Stiess DM. Pharmaceutical composition for the oral administration of poorly soluble drugs comprising an anorphous solid dispersion “EP004119128A1.”. 2023; 1:1–26.

  172. Hoshi N. General pharmacological studies of hydroxypropyl methyl cellulose acetate succinate in experimental animals. J Toxicol Sci. 1985;10(II):129–46. https://doi.org/10.2131/jts.10.supplementii_129.

  173. Hoshi N. Studies of hydroxypropylmethyl cellulose acetate succinate on fertility in rats. J Toxicol Sci. 1985;10(II):187–201. Available from: http://www.mendeley.com/research/geology-volcanic-history-eruptive-style-yakedake-volcano-group-central-japan/. Accessed 5 April 2023.

  174. Hoshi N. Teratological studies of hydroxypropyl methyl cellulose acetate succinate in rats. J Toxicol Sci. 1985;10(II):203–26. Available from: http://www.mendeley.com/research/geology-volcanic-history-eruptive-style-yakedake-volcano-group-central-japan/. Accessed 5 April 2023.

  175. Hoshi N. Teratological study of hydroxypropyl methyl cellulose acetate succinate in rabbits. J Toxicol Sci. 1985;10(II):227–34. Available from: http://www.mendeley.com/research/geology-volcanic-history-eruptive-style-yakedake-volcano-group-central-japan/. Accessed 5 April 2023.

  176. Hoshi N. Effects on offsprings by oral administration of hydroxypropyl cellulose acetate succinate to the female rats in peri and post natal periods. J Toxicol Sci. 1985;10(II):235–55. https://doi.org/10.1128/AAC.48.3.804-808.2004.

  177. Courtney R, Radwanski E, Lim J, Laughlin M. Pharmacokinetics of posaconazole coadministered with antacid in fasting or nonfasting healthy men. Antimicrob Agents Chemother. 2004;48(3):804–8. https://doi.org/10.1128/AAC.48.3.804-808.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Dong Z, Choi DS. Hydroxypropyl methylcellulose acetate succinate: potential drug - excipient incompatibility. AAPS PharmSciTech. 2008;9(3):991–7. https://doi.org/10.1208/s12249-008-9138-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Lu J, Obara S, Ioannidis N, Suwardie J, Gogos C, Kikuchi S. Understanding the processing window of hypromellose acetate succinate for hot-melt extrusion, part i: polymer characterization and hot-melt extrusion. Adv Polym Technol. 2018;37(1):154–66. https://doi.org/10.1002/adv.21652.

    Article  CAS  Google Scholar 

  180. Chen Y, Wang S, Wang S, Liu C, Su C, Hageman M, et al. Sodium lauryl sulfate competitively interacts with HPMC-AS and consequently reduces oral Bioavailability of posaconazole/HPMC-AS amorphous solid dispersion. Mol Pharm. 2016;13(8):2787–95. https://doi.org/10.1021/acs.molpharmaceut.6b00391.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author gratefully acknowledges Colorcon Asia Pvt. Ltd, Goa, India, and is also grateful to the industrial research laboratory, BITS Pilani, Pilani campus.

Author information

Author notes

  1. Sunil Kumar Dubey

    Present address: R&D Healthcare Emami Ltd., Belgharia, Kolkata, 700056, India

  2. Manisha Choudhari and Shantanu Damle contributed equally to this work

Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Vidya Vihar, Pilani Campus, Rajasthan, 333031, India

    Manisha Choudhari, Ranendra Narayan Saha, Sunil Kumar Dubey & Gautam Singhvi

  2. Colorcon Asia Pvt. Ltd. Verna Industrial Estate, Verna, Goa, 403722, India

    Shantanu Damle

Authors
  1. Manisha Choudhari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shantanu Damle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ranendra Narayan Saha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunil Kumar Dubey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gautam Singhvi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Manisha Choudhari and Shantanu Damle: design the review article, interpret the relevant literature, and write and review the original draft; Ranendra Narayan Saha, Sunil Kumar Dubey, and Gautam Singhvi: editing, supervision, and critically revising the review article.

Corresponding authors

Correspondence to Sunil Kumar Dubey or Gautam Singhvi.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 135 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choudhari, M., Damle, S., Saha, R.N. et al. Emerging Applications of Hydroxypropyl Methylcellulose Acetate Succinate: Different Aspects in Drug Delivery and Its Commercial Potential. AAPS PharmSciTech 24, 188 (2023). https://doi.org/10.1208/s12249-023-02645-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-023-02645-1

Keywords

Search

Navigation