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Journal of Pharmaceutical Innovation

, Volume 13, Issue 4, pp 353–366 | Cite as

HPMC-Eudragit-Based Gastro-retentive Hydrodynamically Balanced System—Suitable for Sparingly Soluble and Freely Soluble Drugs: an In Vitro Study

  • Syed Naiem Raza
  • Nisar Ahmad KhanEmail author
Original Article
  • 73 Downloads

Abstract

Purpose

In this study HPMC-eudragit based hydrodynamically balanced capsules of two model drugs; propranolol HCl and ofloxacin were prepared with the aim to have the gastric retention of the systems for longer periods of time with desired sustained/ controlled drug release.

Methods

Gastro-retentive capsules were prepared by simple physical blending of various low density polymers and filling into capsules. These capsules were subjected to in vitro buoyancy/ matrix integrity and dissolution studies. Weight variation, content uniformity test, UV spectral analysis and placebo interaction studies were also performed.

Results

Preliminary studies revealed that high soluble drug required higher polymer ratios to sustain drug release and maintain matrix integrity/ buoyancy than low soluble drug. In both the cases, with increase in HPMC and eudragit S100 levels there was an increase in matrix integrity and decrease in drug release rate, however much higher levels of eudragit S100 decreased matrix integrity and buoyancy. Lactose (release rate modifier) decreased matrix integrity, buoyancy and increased drug release. Mechanism of release in the both cases was found to be anomalous "non-fickian".

Conclusion

From this research and the literature available on the eudragit and HPMC matrix systems, it is evident that different categories of drugs (suitable for gastric retention), ranging from freely soluble to sparingly soluble can be suitably formulated as HPMCeudragit based GR HBS capsules with desired drug release characteristics, provided no chemical instability/ incompatibility occurs between the drug and the polymers.

Keywords

HPMC-eudragit propranolol HCl Ofloxacin freely soluble sparingly soluble gastro retentive 

References

  1. 1.
    Karna S, Chaturvedi S, Agrawal V, Alim M. Formulation approaches for sustained release dosage forms : a review. Asian J Pharm Clin Res. 2015;8:46–53.Google Scholar
  2. 2.
    Garg R, Gupta GD. Progress in controlled gastroretentive delivery systems. Trop J Pharm Res. 2008;7:1055–66.CrossRefGoogle Scholar
  3. 3.
    Isha C, Nimrata S, Rana A, Surbhi G. Oral sustained release drug delivery system: an overview. Int Res J Pharm. 2012;3:57–62.Google Scholar
  4. 4.
    Lopes CM, Bettencourt C, Rossi A, Buttini F, Barata P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int J Pharm Elsevier BV. 2016;510:144–58.CrossRefGoogle Scholar
  5. 5.
    Arunkumar N, Rani C, Mohanraj KP. Formulation and in vitro evaluation of oral floating tablets of atorvastatin calcium. Res J Pharm Tech. 2008;1:492–5.Google Scholar
  6. 6.
    Sayeed A, Kinagi MB, Mohiuddin MH, Gada S, Md Noorulla S. Gastro retentive drug delivery systems: a review. Der Pharm Lett. 2011;3:121–37.Google Scholar
  7. 7.
    Chen YC, Ho HO, Lee TY, Sheu MT. Physical characterizations and sustained release profiling of gastroretentive drug delivery systems with improved floating and swelling capabilities. Int J Pharm [Internet] Elsevier BV. 2013;441:162–9.Google Scholar
  8. 8.
    Raza SN, Khan NA. Role of mathematical modelling in controlled release drug delivery. Int J Med Res Pharm Sci. 2017;4:84–95.Google Scholar
  9. 9.
    Amarjeet D, Ankur R, Seema R, Khan M. Gastroretentive dosage forms: review on floating drug delivery systems. Int Res J Pharm. 2011;2:72–8.Google Scholar
  10. 10.
    Eberle VA, Schoelkopf J, Gane PAC, Alles R, Huwyler J, Puchkov M. Floating gastroretentive drug delivery systems: comparison of experimental and simulated dissolution profiles and floatation behavior. Eur J Pharm Sci. 2014;58:34–43.CrossRefGoogle Scholar
  11. 11.
    Streubel A, Siepmann J, Bodmeier R. Drug delivery to the upper small intestine window using gastroretentive technologies. Curr Opin Pharmacol. 2006;6:501–8.CrossRefGoogle Scholar
  12. 12.
    Garg R, Gupta GD. Preparation and evaluation of gastroretentive floating tablets of acyclovir. Curr Drug Deliv. 2009;6:437–43.CrossRefGoogle Scholar
  13. 13.
    Chinthala CSK, Kota KSR, Hadassah M, Metilda EH, Sridevi S. Formulation and evaluation of gastroretentive floating tablets of gabapentin using effervescent technology. Int J Pharm Biomed Res. 2012;3:202–8.Google Scholar
  14. 14.
    Eisenacher F, Garbacz G, Mader K. Physiological relevant in vitro evaluation of polymer coats for gastroretentive floating tablets. Eur J Pharm Biopharm. 2014;88:778–86.CrossRefGoogle Scholar
  15. 15.
    Nayak AK, Maji R, Das B. Gastroretentive drug delivery systems: a review. Asian J Pharm Clin Res. 2010;3:2–10.Google Scholar
  16. 16.
    Raza S, Khan N. Gastric retention—an innovative approach to increase bioavailability. International J. Biol Pharm allied Sci 2014;3:113–133. Available from: www.ijbpas.com
  17. 17.
    Rednick AB, Tucker SJ. Sustained release bolus for animal husbandry. United States Patent. 1970;3507952:1–7.Google Scholar
  18. 18.
    Davis SS, Stockwell AF, Taylor MJ, Hardy JG, Whalley DR, Wilson CG, et al. The effect of density on the gastric emptying of single- and multiple-unit dosage forms. Pharm Res. 1986;3:214–7.CrossRefGoogle Scholar
  19. 19.
    Mamajek R, Moyer ES. Drug dispensing device and method. United States Patent 4207890. 1980.Google Scholar
  20. 20.
    Urquhart J, Theeuwes F. Drug delivery system comprising a reservoir containing a plurality of tiny pills United States Patent 4434153. 1984Google Scholar
  21. 21.
    Ponchel G, Irachi J. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev. 1998;1:191–219.CrossRefGoogle Scholar
  22. 22.
    Fix J, Cargill R, Engle K. Controlled gastric emptying. III. Gastric residence time of a nondisintegrating geometric shape in human volunteers. Pharm Res. 1993;10:1087–9.CrossRefGoogle Scholar
  23. 23.
    Kedzierewicz F, Thouvenot P, Lemut J, Etienne A, Hoffman M, Maincent P. Evaluation of peroral silicone dosage forms in humans by gamma-scintigraphy. J Control Release. 1999;58:195–205.CrossRefGoogle Scholar
  24. 24.
    Deshpande A, Shah NH, Rhodes TC, Malick W. Development of a novel controlled release system for gastric retention. Pharm Res. 1997;14:815–9.CrossRefGoogle Scholar
  25. 25.
    Groning R, Heun G. Oral dosage forms with controlled gastrointestinal transit. Drug Dev Ind Pharm. 1984;10:527–39.CrossRefGoogle Scholar
  26. 26.
    Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Control Release. 2000;63:235–59.CrossRefGoogle Scholar
  27. 27.
    Sheth PR, Tossounian J. The hydrodynamically balanced system: a novel drug delivery system for oral use. Drug Dev Ind Pharm. 1984;10:313–39.CrossRefGoogle Scholar
  28. 28.
    Shahwal VK, Upadhyay A. Gastro retentive floating drug delivery systems. Int J Biomed Res. 2011;2:381–90.Google Scholar
  29. 29.
    Park K. Absence of in vivo–in vitro correlation in per-oral drug delivery. J Control Release. Elsevier B.V.; 2014;180:150. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0168365914001631 CrossRefGoogle Scholar
  30. 30.
    Al-Omar MA. Profiles of drug substances, excipients and related methodology. Elsevier Inc. 2009;34:265–98.Google Scholar
  31. 31.
    Eddington ND, Ashraf M, Augsburger LL, Leslie JL, Fossler MJ, Lesko LJ, et al. Identification of formulation and manufacturing variables that influence in vitro dissolution and in vivo bioavailability of propranolol hydrochloride tablets. Pharm Dev Technol. 1998;3:535–47.CrossRefGoogle Scholar
  32. 32.
    Zhang C, Xu M, Tao X, Tang J, Liu Z, Zhang Y, et al. A floating multiparticulate system for ofloxacin based on a multilayer structure: in vitro and in vivo evaluation. Int J Pharm. 2012;430:141–50.CrossRefGoogle Scholar
  33. 33.
    Chavanpatil M, Jain P, Chaudhari S, Shear R, Vavia P. Development of sustained release gastroretentive drug delivery system for ofloxacin: in vitro and in vivo evaluation. Int J Pharm. 2005;304:178–84.CrossRefGoogle Scholar
  34. 34.
    Ding J, Lu G, Lee S, Nie Y, Liu J. Biological fate and effects of propranolol in an experimental aquatic food chain. Sci Total Environ. 2015;532:31–9.CrossRefGoogle Scholar
  35. 35.
    Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS PharmSciTech. 2009;10:1071–9.CrossRefGoogle Scholar
  36. 36.
    Venkata Srikanth M, Sreenivasa Rao N, Ambedkar Sunil S, Janaki Ram B, Kolapalli VRM. Statistical design and evaluation of a propranolol HCl gastric floating tablet. Acta Pharm Sin B. 2012;2:60–9.CrossRefGoogle Scholar
  37. 37.
    Cheng C, Wu PC, Lee HY, Hsu KY. Development and validation of an in vitroein vivo correlation (IVIVC) model for propranolol hydrochloride extended-release matrix formulations. J Food Drug Anal. 2014;22:257–63.CrossRefGoogle Scholar
  38. 38.
    Davis SS. Formulation strategies for absorption windows. Drug Discov Today. 2005;10:249–57.CrossRefGoogle Scholar
  39. 39.
    Reddy AB, Rani BS, Tony DE, Raja DS, Sindhura L, Kumar NS, et al. Aceclofenac floating tablets—a promising sustained release dosage form. Int J Drug Dev Res. 2011;3:290–300.Google Scholar
  40. 40.
    Ali J, Arora S, Ahuja A, Babbar AK, Sharma RK, Khar RK, et al. Formulation and development of hydrodynamically balanced system for metformin: in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2007;67:196–201.CrossRefGoogle Scholar
  41. 41.
    Raza SN, Khan NA. Various formulation variables effecting floatation behaviour of single unit gastroretentive capsules of ofloxacin. Int J Pharm Pharm Sci. 2017;9:213–7.CrossRefGoogle Scholar
  42. 42.
    Chen G-L, Hao W-H. Factors affecting zero-order release kinetics of porous gelatine capsules. Drug Dev Ind Pharm. 1998;24:557–62.CrossRefGoogle Scholar
  43. 43.
    Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–33.CrossRefGoogle Scholar
  44. 44.
    Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–5.CrossRefGoogle Scholar
  45. 45.
    Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35.CrossRefGoogle Scholar
  46. 46.
    Gahiwade HP, Patil MV, Tekade BW, Thakare VM, Patil VR. Formulation and in-vitro evaluation of trifluoperazine hydrochloride bilayer floating tablet. Int J Pharm Biol Sci. 2012;2:166–72.Google Scholar
  47. 47.
    Ahmed NR. Ultraviolet spectrophotometric determination of trifluoperazine HCl in pharmaceutical preparations and environmental wastewater samples: application to content uniformity testing. Res Rev J Pharm Anal. 2014;3:30–4.Google Scholar
  48. 48.
    Mogal RT, Galgatte UC, Chaudhari PD. Floating pulsatile drug delivery of ranitidine hydrochloride for nocturnal acid breakthrough: design, optimization, in vitro and in vivo evaluation. Int J Pharm Pharm Sci. 2013;5:722–7.Google Scholar
  49. 49.
    Punitha K, Khadhir S, Ravichandiran V, Umadevi SK, Vaijayanthi V, Padmapriya S, et al. Intragastric floating drug delivery system of ranitidine hydrochloride : formulation and evaluation. Int J Pharm Pharm Sci. 2010;2:105–8.Google Scholar
  50. 50.
    Pahwa R, Sharma S, Kumar V, Kohli K. Ranitidine hydrochloride: an update on analytical, clinical and pharmacological aspects. J Chem Pharm Res. 2016;8:70–8.Google Scholar
  51. 51.
    Katakam VK, Reddy S, Panakanti PK, Yamsani MR. Design and evaluation of a novel gas formation-based multiple-unit gastro-retentive floating drug delivery system for quetiapine fumarate. Trop J Pharm Res. 2014;13:489–96.CrossRefGoogle Scholar
  52. 52.
    Bagade SB, Narkhede SP, Nikam DS, Sachde CK. Development and validation of UV spectrophotometric method for determination of quetiapine fumarate in two different dose tablets. Int J ChemTech Res. 2009;1:898–904.Google Scholar
  53. 53.
    Kumar DA, Satyabrata B, Kumar HD, Srilakshmi N, Pranali P. Formulation design and in-vitro evaluation of antipsychotic drug quetiapine fumarate. Int J Res Ayurveda Pharm. 2013;4:266–71.CrossRefGoogle Scholar
  54. 54.
    Shah S, Pandya S, Waghulade M. Development and investigation of gastro retentive dosage form of weakly basic drug. Asian J Pharm. 2010;4:11–6.CrossRefGoogle Scholar
  55. 55.
    Aboutaleb A, Abdel-Rahman S, Ahmed M, Younis M. Improvement of domperidone solubility and dissolution rate by dispersion in various hydrophilic carriers. J Appl Pharm Sci. 2016;6:133–9.CrossRefGoogle Scholar
  56. 56.
    Guleria R, Sharma V, Kapoor A, Kaith NS, Singh R. Polyethylene glycol enhances solubility of domperidone through solid dispersion. Am J Pharmatech Res. 2012;2:629–38.Google Scholar
  57. 57.
    Chauhan R, Arjariya P, Singh G, Sharma N. Floating tablets: a single unit approach to increase the gastroretention of cefpodoxime proxetil. Curr Res Pharm Sci. 2014;4:87–91.Google Scholar
  58. 58.
    Kakumanu VK, Arora VK, Bansal AK. Gastro-retentive dosage form for improving bioavailability of cefpodoxime proxetil in rats. Yakugaku Zasshi. 2008;128:439–45.CrossRefGoogle Scholar
  59. 59.
    Ganesan V, Kanth VSVSPK. Preparation and in vitro evaluation of microballoon drug delivery system of telmisartan. Int J Pharm Sci Drug Res. 2013;5:141–5.Google Scholar
  60. 60.
    Kausalya J, Suresh K, Padmapriya S, Rupenagunta A, Senthilnathan B. Solubility and dissolution enhancement profile of telmisartan using various techniques. Int J PharmTech Res. 2011;3:1737–49.Google Scholar
  61. 61.
    Nanjan C, Venkatesh JS, Santhosh RM, Rabadia J, Patil S, Shankraiah V. Intragastric floating drug delivery system of levofloxacin: formulation and evaluation. J Pharm Sci Res. 2011;3:1265–8.Google Scholar
  62. 62.
    Gevariya H, Dharamsi A, Girhepunje K, Pal R. Once a day ocular inserts for sustained delivery of levofloxacin: design, formulation and evaluation. Asian J Pharm. 2009;3:314–8.CrossRefGoogle Scholar
  63. 63.
    Senthil A, Kumar PS, Raju CN, Mohideen S. Formulation and evaluation of gastric oral floating tablet of glipizide. Int J Biol Pharm Res. 2010;1:108–13.Google Scholar
  64. 64.
    Saumya D, Dharmajit P. Formulation and optimisation of gastro retentive drug delivery system containing glipizide. Int J Pharm Pharm Sci. 2012;4:203–5.Google Scholar
  65. 65.
    Shukla M, Rathore P, Jain A, Nayak S. Enhanced solubility study of glipizide using different solubilization techniques. Int J Pharm Pharm Sci. 2010;2:46–8.Google Scholar
  66. 66.
    Thombre AG, DeNoto AR, Gibbes DC. Delivery of glipizide from asymmetric membrane capsules using encapsulated excipients. J Control Release. 1999;60:333–41.CrossRefGoogle Scholar
  67. 67.
    Apparao B, Shivalingam MR, Reddy YVK, Rao S, Rajesh K, Sunitha N. Formulation and evaluation of aceclofenac solid dispersions for dissolution rate enhancement. Int J Pharm Sci Drug Res. 2010;2:146–50.Google Scholar
  68. 68.
    Cheong LWS, Heng PWS, Wong LF. Relationship between polymer viscosity and drug release from a matrix system. Pharm Res. 1992;9:1510–4.CrossRefGoogle Scholar
  69. 69.
    Sumathi S, Ray AR. Role of modulating factors on release of caffeine from tamarind seed polysaccharide tablets. Trends Biomater Artif Organs. 2003;17:41–6.Google Scholar
  70. 70.
    Ford JL, Rubinstein MH, Hogan JE. Propranolol hydrochloride and aminophylline release from matrix tablets containing hydroxypropylmethylcellulose. Int J Pharm. 1985;24:339–50.CrossRefGoogle Scholar
  71. 71.
    Lee B-J, Ryu S-G, Cui J-H. Formulation and release characteristics of hydroxypropyl methylcellulose matrix tablet containing melatonin. Drug Dev Ind Pharm. 1999;25:493–501.CrossRefGoogle Scholar
  72. 72.
    Prasanthi NL, Manikiran SS, Rama RN. Effect of solubility of the drug on the release kinetics from hydrophilic matrices. Int J PharmTech Res. 2010;2:2506–11.Google Scholar
  73. 73.
    Chakraborty S, Khandai M, Sharma A, Patra CN, Patro VJ, Sen KK. Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from HPMC based matrix formulations. Acta Pharma. 2009;59:313–23.CrossRefGoogle Scholar
  74. 74.
    Tiwari S, Rajabi-Siahboomi AR. Modulation of drug release from hydrophilic matrices. Pharm Technol Eur. 2008;20:24–32.Google Scholar
  75. 75.
    Jamzad S, Fassihi R. Development of a controlled release low dose class II drug-glipizide. Int J Pharm. 2006;312:24–32.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of Applied Science and TechnologyUniversity of KashmirSrinagarIndia

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