Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Enhanced Mefenamic Acid Release from Poloxamer-Silicon Dioxide Gel Filled in Hard Gelatin Capsules - An Application of Liquid Semisolid Matrix Technology for Insoluble Drug

Author(s): Misbah Sultana, Safia Sultana, Khalid Hussain, Tariq Saeed, Mobashar Ahmad Butt, Syed Atif Raza, Rizwan Mahmood, Saeed Hassan, Ubaid Ullah Anwer and Nadeem Irfan Bukhari*

Volume 19, Issue 7, 2022

Published on: 11 January, 2022

Page: [801 - 811] Pages: 11

DOI: 10.2174/1567201818666210903152618

Price: $65

Abstract

Introduction: Liquid Semisolid Matrix (LSSM) technology involves the filling of drugmixed gel in hard gelatin capsules for different applications.

Methods: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO2.

Results: Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO2 gels, both with first-order kinetics. In 12 month long-term stability studies, only mefenamic acid-L64- SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. No chemical drug-polymer interactions were found in FTIR.

Conclusion: The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO2.

Keywords: Liquid semisolid matrix, mefenamic acid, aerosil® A200, poloxamer, rheology, thixotropy.

« Previous
Graphical Abstract

[1]
Ellison, M.; Rowley, G.; Walters, P.; Barnes, D. Release of drug from gel thixotropic triglyceride formulations, liquid filled in hard gelatin capsules. Proc. Pharm. Tech. Conf., 1995, p. 91.
[2]
Ellison, M.; Rowley, G.; Walters, P.; Coupe, A. The effect of mechanical mixing on gel rheology for liquid-fill hard gelatin capsule formulations. Pharm. Technol., 1996, pp. 102-110.
[3]
Saeed, T. Rheological characterization of poloxamer/silicon dioxide gels for liquid filled hard gelatin capsules; Ph D. thesis, University of Sunderland: UK, 1999.
[4]
Lee, C.H.; Moturi, V.; Lee, Y. Thixotropic property in pharmaceutical formulations. J. Control. Release, 2009, 136(2), 88-98.
[http://dx.doi.org/10.1016/j.jconrel.2009.02.013] [PMID: 19250955]
[5]
Sultana, M.; Saeed-Ul-Hassan, S.; Saeed, T.; Mahmood, R.; Tariq, I.; Shah, P.A.; Syed, A. The effect of silicon dioxide concentrations on drug release from poloxamer/silicon dioxide gel formulations and their rheological characterization. Lat. Am. J. Pharm., 2013, 32(6), 911-917.
[6]
Sultana, M.; Butt, M.A.; Saeed, T.; Mahmood, R.; Ul Hassan, S.; Hussain, K.; Raza, S.A.; Ahsan, M.; Bukhari, N.I. Effect of rheology and poloxamers properties on release of drugs from silicon dioxide gel-filled hard gelatin capsules-a further enhancement of viability of liquid semisolid matrix technology. AAPS PharmSciTech., 2017, 18(6), 1998-2010.
[http://dx.doi.org/10.1208/s12249-016-0674-0] [PMID: 27933585]
[7]
Walters, P.; Rowley, G.; Pearson, J.; Taylor, C. Formulation and physical properties of thixotropic gels for hard gelatin capsules. Drug Dev. Ind. Pharm., 1992, 18(15), 1613-1631.
[http://dx.doi.org/10.3109/03639049209040890]
[8]
Djimbo, M.; Moës, A.J. Release of drugs formulated as hard pastes filled into hard gelatin capsules. Part 1. Physical properties and in vitro testing. J. Pharm. Belg., 1984, 39(1), 36-42.
[PMID: 6726605]
[9]
Hawley, A.; Rowley, G.; Lough, W.; Chatham, S. Physical and chemical characterization of thermosoftened bases for molten filled hard gelatin capsule formulations. Drug Dev. Ind. Pharm., 1992, 18(16), 1719-1739.
[http://dx.doi.org/10.3109/03639049209040898]
[10]
Cade, D.; Cole, E.; Mayer, J.P.; Wittwer, F. Liquid filled and sealed hard gelatin capsules. Drug Dev. Ind. Pharm., 1986, 12(11-13), 2289-2300.
[http://dx.doi.org/10.3109/03639048609042636]
[11]
Jones, B.E. Hard gelatin capsules and pharmaceutical formulation. Pharm. Technol., 1985, 9, 106-112.
[12]
Rowley, G. Filling of liquids and semi solids into two piece capsulespharmaceutical capsules; Pharmaceutical press: UK, 2004.
[13]
Bhawna, B.; Agrawal, S. capsules In: Pharmaceutical Technology; Delhi Institute of Pharmaceutical Science and the Research Sector: Pushp Vihar, New Delhi, 2008; pp. 1-26.
[14]
Smith, A.; Lampard, J.; Carruthers, K.; Regan, P. The filling of molten ibuprofen into hard gelatin capsules. Int. J. Pharm., 1990, 59(2), 115-119.
[http://dx.doi.org/10.1016/0378-5173(90)90085-I]
[15]
Kattige, A.; Rowley, G. The effect of poloxamer viscosity on liquid-filling of solid dispersions in hard gelatin capsules. Drug Dev. Ind. Pharm., 2006, 32(8), 981-990.
[http://dx.doi.org/10.1080/03639040600559081] [PMID: 16954111]
[16]
Das, S.; Samanta, A.; Bose, A. Design, development and evaluation of fluconazole topical gel. Asian J. Pharm. Clin. Res., 2015, 8(2), 132-135.
[17]
Zhang, J.; Zhang, L.; Gong, X. Large-scale spraying fabrication of robust fluorine-free superhydrophobic coatings based on dual- sized silica particles for effective antipollution and strong buoyancy. Langmuir, 2021, 37(19), 6042-6051.
[http://dx.doi.org/10.1021/acs.langmuir.1c00706] [PMID: 33939432]
[18]
Zhong, L.; Tao, H.; Gong, X. Superhydrophobic poly(l-lactic acid) membranes with fish-scale hierarchical microstructures and their potential application in oil-water separation. Langmuir, 2021, 37(22), 6765-6775.
[http://dx.doi.org/10.1021/acs.langmuir.1c00858] [PMID: 34029095]
[19]
Korsmeyer, R.W.; Gurny, R.; Doelker, E.; Buri, P.; Peppas, N.A. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm., 1983, 15(1), 25-35.
[http://dx.doi.org/10.1016/0378-5173(83)90064-9]
[20]
Higuchi, T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52(12), 1145-1149.
[http://dx.doi.org/10.1002/jps.2600521210] [PMID: 14088963]
[21]
Moffat, A.C.; Osselton, M.D.; Widdop, B.; Watts, J. (eds). Clarke's analysis of drugs and poisons, 4th edn. Pharmaceutical Press: London, 2011.
[22]
Benedict, T.; Rowley, G.; Walters, P. The effect of silicon dioxide concentration on drug release from triglyceride gel formulations, liquid filled in hard gelatin capsules. Pharmaceutical Technolog Conference, Pharmaceutical Technology, 1997, pp. 237-241.
[23]
BASF. Pluronic® PE types; Technical information, 2002. Available from: file:///C:/Users/Sumaiya/Downloads/Pluronic_PE_Types_2014%20(1).pdf pp. 811.
[24]
British-Pharmacopoeia. British pharmacopoeia 2000; Bernan Press: PA, 2000, Vol. 1.
[25]
Roy, D.; Das, S.; Samanta, A. Design and in vitro release kinetics of liposomal formulation of acyclovir. Int. J. Appl. Pharmaceut., 2019, 11(6), 61-65.
[http://dx.doi.org/10.22159/ijap.2019v11i6.34917]
[26]
Martin, A.N. Martin’s physical pharmacy and pharmaceutical sciences: Physical chemical and biopharmaceutical principles in the pharmaceutical sciences; Lippincott Williams & Wilkins, 2006.
[27]
Sweetman, S. C. Martindale: The complete drug reference; Pharmaceutical Press: London, 2014.
[28]
Walters, P.; Rowley, G.; Pearson, J.; Tayler, C. In vitro drug release by colloidal silicon dioxide in a semisolid matrix hard gelatin capsule formulation, int symp control rel bioact mater. , 1991; p. 65.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy