Abstract
The aim of this study was to evaluate the potential of a cross-linked pregelatinized potato starch (PREGEFLO® PI10) as matrix former for controlled release tablets. Different types of tablets loaded with diprophylline, diltiazem HCl or theophylline were prepared by direct compression of binary drug/polymer blends. The drug content was varied from 20 to 50%. Two hydroxypropyl methylcellulose grades (HPMC K100LV and K100M) were studied as alternative matrix formers. Drug release was measured in a variety of release media using different types of experimental set-ups. This includes 0.1 N HCl, phosphate buffer pH 6.8 and water, optionally containing different amounts of NaCl, sucrose, ethanol or pancreatin, fasted state simulated gastric fluid, fed state simulated gastric fluid, fasted state simulated intestinal fluid, fed state simulated intestinal fluid as well as media simulating the conditions in the colon of healthy subjects and patients suffering from Crohn’s disease. The USP apparatuses I/II/III were used under a range of operating conditions and optionally coupled with the simulation of additional mechanical stress. Importantly, the drug release kinetics was not substantially affected by the investigated environmental conditions from tablets based on the cross-linked pregelatinized potato starch, similar to HPMC tablets. However, in contrast to the latter, the starch-based tablets roughly kept their shape upon exposure to the release media (they “only” increased in size) during the observation period, and the water penetration into the systems was much less pronounced. Thus, the investigated cross-linked pregelatinized potato starch offers an interesting potential as matrix former in controlled release tablets.
Similar content being viewed by others
References
Maderuelo C, Zarzuelo A, Lanao JM. Critical factors in the release of drugs from sustained release hydrophilic matrices. J Control Release. 2011;154(1):2–19.
Zhang X, Li Y, Huang Z, Cui Y, Zhao Z, Yue X, et al. Development and pharmacokinetics evaluation of quetiapine fumarate sustained-release tablets based on hydrophilic matrix. J Drug Deliv Sci Technol. 2019;54:101322.
Li CL, Martini LG, Ford JL, Roberts M. The use of hypromellose in oral drug delivery. J Pharm Pharmacol. 2005;57(5):533–46.
Ward A, Walton K, Mawla N, Kaialy W, Liu L, Timmins P, et al. Development of a novel method utilising dissolution imaging for the measurement of swelling behaviour in hydrophilic matrices. Int J Pharmaceut X. 2019;1:100013.
Lenaerts V, Moussa I, Dumoulin Y, Mebsout F, Chouinard F, Szabo P, et al. Cross-linked high amylose starch for controlled release of drugs: recent advances. J Control Release. 1998;53(1):225–34.
Hattori Y, Takaku T, Otsuka M. Mechanochemical effect on swelling and drug release of natural polymer matrix tablets by X-ray computed tomography. Int J Pharm. 2018;539(1):31–8.
Xu X, Siddiqui A, Srinivasan C, Mohammad A, Rahman Z, Korang-Yeboah M, et al. Evaluation of abuse-deterrent characteristics of tablets prepared via hot-melt extrusion. AAPS PharmSciTech. 2019;20(6):230.
Siepmann F, Eckart K, Maschke A, Kolter K, Siepmann J. Modeling drug release from PVAc/PVP matrix tablets. J Control Release. 2010;141(2):216–22.
Lazzari A, Kleinebudde P, Knop K. Xanthan gum as a rate-controlling polymer for the development of alcohol resistant matrix tablets and mini-tablets. Int J Pharm. 2018;536(1):440–9.
Vlachou M, Tragou K, Siamidi A, Kikionis S, Chatzianagnostou A-L, Mitsopoulos A, et al. Modified in vitro release of the chronobiotic hormone melatonin from matrix tablets based on the marine sulfated polysaccharide ulvan. J Drug Deliv Sci Technol. 2018;44:41–8.
Layek B, Mandal S. Natural polysaccharides for controlled delivery of oral therapeutics: a recent update. Carbohydr Polym. 2019;115617.
Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2001;48(2):139–57.
Borgquist P, Körner A, Piculell L, Larsson A, Axelsson A. A model for the drug release from a polymer matrix tablet—effects of swelling and dissolution. J Control Release. 2006;113(3):216–25.
Kaunisto E, Abrahmsen-Alami S, Borgquist P, Larsson A, Nilsson B, Axelsson A. A mechanistic modelling approach to polymer dissolution using magnetic resonance microimaging. J Control Release. 2010;147(2):232–41.
Siepmann J, Karrout Y, Gehrke M, Penz FK, Siepmann F. Predicting drug release from HPMC/lactose tablets. Int J Pharm. 2013;441(1):826–34.
Controlled release tablets based on HPMC:lactose blends. Pharma Excip [Internet]. 2019. [cited 2019 Nov 27]; Available from: https://www.pharmaexcipients.com/oral-excipients/hpmclactose-blends/.
Xi Z, Sharma N, Paprikar A, Lin S. Development and evaluation of dipyridamole sustained release tablets containing micro-environmental pH modifiers. J Drug Deliv Sci Technol. 2019;54:101231.
Panainte AD, Gafitanu C, Stoleriu I, Tarțău LM, Popescu M-C, Lisa G, et al. New modified release tablets of bisoprolol fumarate for the treatment of hypertension: characterization and in vitro evaluation. J Drug Deliv Sci Technol. 2019;50:402–9.
Krkobabić M, Medarević D, Cvijić S, Grujić B, Ibrić S. Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: impact on internal structure and drug dissolution rate. Int J Pharm. 2019;572:118790.
Cui M, Yang Y, Jia D, Li P, Li Q, Chen F, et al. Effect of novel internal structures on printability and drug release behavior of 3D printed tablets. J Drug Deliv Sci Technol. 2019;49:14–23.
Yi S, Wang J, Lu Y, Ma R, Gao Q, Liu S, et al. Novel hot melt extruded matrices of hydroxypropyl cellulose and amorphous felodipine–plasticized hydroxypropyl methylcellulose as controlled release systems. AAPS PharmSciTech. 2019;20(6):219.
Caccavo D, Lamberti G, Barba AA, Abrahmsén-Alami S, Viridén A, Larsson A. Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study. Int J Pharm. 2017;528(1):705–13.
Zhu C, Xu S, Han X. Sustained release bilayer tablet of ibuprofen and phenylephrine hydrochloride: preparation and pharmacokinetics in beagle dogs. AAPS PharmSciTech. 2019;20(2):86.
Ashogbon AO, Akintayo ET. Recent trend in the physical and chemical modification of starches from different botanical sources: a review. Starch - Stärke. 2014;66(1–2):41–57.
Hong Y, Liu G, Gu Z. Recent advances of starch-based excipients used in extended-release tablets: a review. Drug Deliv. 2016;23(1):12–20.
Te Wierik GHP, Eissens AC, Bergsma J, Arends-Scholte AW, Bolhuis GK. A new generation starch product as excipient in pharmaceutical tablets: III. Parameters affecting controlled drug release from tablets based on high surface area retrograded pregelatinized potato starch. Int J Pharm. 1997;157(2):181–7.
Yoon H-S, Lee JH, Lim S-T. Utilization of retrograded waxy maize starch gels as tablet matrix for controlled release of theophylline. Carbohydr Polym. 2009;76(3):449–53.
Onofre FO, Mendez-Montealvo G, Wang Y-J. Sustained release properties of cross-linked corn starches with varying amylose contents in monolithic tablets. Starch - Stärke. 2010;62(3–4):165–72.
Recife ACD, Meneguin AB, Cury BSF, Evangelista RC. Evaluation of retrograded starch as excipient for controlled release matrix tablets. J Drug Deliv Sci Technol. 2017;40:83–94.
Ravenelle F, Rahmouni M. Contramid®: high-amylose starch for controlled drug delivery. In: Polysaccharides for drug delivery and pharmaceutical applications. American Chemical Society (ACS Symposium Series; vol. 934); 2006. p. 79–104. Available from: https://doi.org/10.1021/bk-2006-0934.ch004.
Takieddin M, Fassihi R. A novel approach in distinguishing between role of hydrodynamics and mechanical stresses similar to contraction forces of GI tract on drug release from modified release dosage forms. AAPS PharmSciTech. 2014;16(2):278–83.
Vrbanac H, Krese A. The influence of different mechanical stress on the release properties of HPMC matrix tablets in sucrose-NaCl media. J Drug Deliv Sci Technol. 2019;54:101246.
Parojčić J, Vasiljević D, Ibrić S, Djurić Z. Tablet disintegration and drug dissolution in viscous media: Paracetamol IR tablets. Int J Pharm. 2008;355(1):93–9.
Klein S. The use of biorelevant dissolution media to forecast the in vivo performance of a drug. AAPS J. 2010;12(3):397–406.
Nokhodchi A, Asare-Addo K. Drug release from matrix tablets: physiological parameters and the effect of food. Expert Opin Drug Deliv. 2014;11(9):1401–18.
Koziolek M, Kostewicz E, Vertzoni M. Physiological considerations and in vitro strategies for evaluating the influence of food on drug release from extended-release formulations. AAPS PharmSciTech. 2018;19(7):2885–97.
Fredriksson H, Bjorck I, Andersson R, Liljeberg H. Studies on α-amylase degradation of retrograded starch gels from waxy maize and high-amylopectin potato - ScienceDirect. Carbohydr Polym. 2000;43(1):81–7.
Cai L, Shi Y-C, Rong L, Hsiao BS. Debranching and crystallization of waxy maize starch in relation to enzyme digestibility. Carbohydr Polym. 2010;81(2):385–93.
Rahmouni M, Chouinard F, Nekka F, Lenaerts V, Leroux JC. Enzymatic degradation of cross-linked high amylose starch tablets and its effect on in vitro release of sodium diclofenac. Eur J Pharm Biopharm. 2001;51(3):191–8.
Rubbens J, Brouwers J, Wolfs K, Adams E, Tack J, Augustijns P. Ethanol concentrations in the human gastrointestinal tract after intake of alcoholic beverages. Eur J Pharm Sci. 2016;86:91–5.
Hsein H, Garrait G, Tamani F, Beyssac E, Hoffart V. Denatured whey protein powder as a new matrix excipient: design and evaluation of mucoadhesive tablets for sustained drug release applications. Pharm Res. 2017;34(2):365–77.
Onofre FO, Wang Y-J. Hydroxypropylated starches of varying amylose contents as sustained release matrices in tablets. Int J Pharm. 2010;385(1–2):104–12.
Jantratid E, Janssen N, Reppas C, Dressman JB. Dissolution media simulating conditions in the proximal human gastrointestinal tract: an update. Pharm Res. 2008;25(7):1663–76.
Baxevanis F, Kuiper J, Fotaki N. Strategic drug analysis in fed-state gastric biorelevant media based on drug physicochemical properties. Eur J Pharm Biopharm. 2018;127:326–41.
Karrout Y, Neut C, Wils D, Siepmann F, Deremaux L, Dubreuil L, et al. Colon targeting with bacteria-sensitive films adapted to the disease state. Eur J Pharm Biopharm. 2009;73(1):74–81.
Siepmann F, Karrout Y, Gehrke M, Penz FK, Siepmann J. Limited drug solubility can be decisive even for freely soluble drugs in highly swollen matrix tablets. Int J Pharm. 2017;526(1–2):280–90.
Siepmann J, Siepmann F. Sink conditions do not guarantee the absence of saturation effects. Int J Pharm. 2020;577:119009.
Funding
This project has received funding from the Interreg 2 Seas programme 2014-2020, co-funded by the European Regional Development Fund under subsidy contract 2S01-059_IMODE.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Several co-authors of this article are employees of the company Roquette, commercializing the investigated starch derivative.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Elgaied-Lamouchi, D., Descamps, N., Lefèvre, P. et al. Robustness of Controlled Release Tablets Based on a Cross-linked Pregelatinized Potato Starch Matrix. AAPS PharmSciTech 21, 148 (2020). https://doi.org/10.1208/s12249-020-01674-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1208/s12249-020-01674-4