DEVELOPMENT AND CHARACTERIZATION OF NEVIRAPINE LOADED AMORPHOUS SOLID DISPERSIONS FOR SOLUBILITY ENHANCEMENT
DOI:
https://doi.org/10.22159/ajpcr.2019.v12i18.34097Keywords:
Nevirapine, Vitamin E tocopherol polyethylene glycol succinate, Solid dispersion, Fast dissolving tabletsAbstract
Objective: The present study entails the development of nevirapine (NVP)-loaded solid dispersions for improvement of solubility and in vitro profile.
Methods: Solid dispersions were prepared through blending with a hydrophilic polymer and Vitamin E tocopherol polyethylene glycol succinate (TPGS) using the solvent evaporation method. The optimized formulations were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and morphological investigations by scanning electron microscopy. The optimized formulation was converted into fast dissolving tablets (FDTs) through direct compression technique and was characterized for pre- and post-compression parameters. Both amorphous dispersions and FDTs were evaluated for in vitro drug release.
Results: NVP showed pH-dependent solubility in different pH media. Above 0.002% w/v Vitamin E TPGS, a linear relationship was observed between the NVP solubility and Vitamin E TPGS concentration. According to the study, the most suitable formulation was NVP:Vitamin E TPGS (1:0.75) in 30 ml solvent with a drug release of 82.96% in 2 h. The analysis of dissolution data of optimized formulation indicated the best fitting with the Higuchi model. FDTs exhibited faster drug release of about 50% in 5 min indicating desired attributes for the immediate dosage form.
Conclusion: The present study vouches for better in vitro profile of NVP from solid dispersion based FDTs.
Downloads
References
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000;50:47-60.
Muller RH, Jacobs C, Kayer O. Nanosuspensions for the Formulation of Poorly Soluble Drugs in Pharmaceutical Emulsion and Suspension. 3rd ed. New York, USA: Marcel Dekker; 2000.
Ghareeb MM, Abdulrasool AA, Hussein AA, Noordin MI. Kneading technique for preparation of binary solid dispersion of meloxicam with poloxamer 188. AAPS Pharm Sci Tech 2009;10:1206-15.
Qian F, Wang J, Hartley R, Tao J, Haddadin R, Mathias N, et al. Solution behavior of PVP-VA and HPMC-AS-based amorphous solid dispersions and their bioavailability implications. Pharm Res 2012;29:2765-76.
Kumar A, Sahoo SK, Padhee K, Kochar PS, Sathapathy A, Pathak N. Review on solubility enhancement techniques for hydrophobic drugs. Pharma Glob 2011;3:1-7.
Budavari S, editor. The Merck Index, an Encyclopedia of Chemicals, Drugs, and Biologicals. Rahway: Merck; 2000. p. 1114.
Sokol RJ, Johnson KE, Karrer FM, Narkewicz MR, Smith D, Kam I. Improvement of cyclosporine absorption in children after liver transplantation by means of water-soluble Vitamin E. Lancet 1991;338:212-5.
Yadav S, Veena M, Srinivas M. Solid dispersion technique to enhance the solubility and dissolution rate of aripiprazole by fusion method. Int J Pharm Pharm Sci 2016;8:187-92.
Mohanraj P, Sarkar DK, Choudhury T, Gauthaman K. A simple and rapid RP-HPLC method for the estimation of NVP in bulk and pharmaceutical dosage forms. J Chem 2008;5:1081-6.
Lokamatha KM, Bharathi A, Kumar SM, Rama, RN. Effect of PVPk30 on complexation and dissolution rate of NVP β-cyclodextrin complexes. Int J Pharm Sci 2008;2:4-13.
Shah I, Bhatt S, Yadav A. Enhancement of solubility and dissolution of nebivolol by solid dispersion technique. Int J Pharm Pharm Sci 2014;6:566-71.
Sarkar M, Khandavilli S, Panchagnula R. Development and validation of RP-HPLC and ultraviolet spectrophotometric methods of analysis for the quantitative estimation of antiretroviral drugs in pharmaceutical dosage forms. J Chromatogr B 2006;830:349-54.
Tachibana T, Nakamura A. Method for preparing an aqueous colloidal dispersion of organic materials by using water-soluble polymers: Dispersion of β-carotene by polyvinylpyrrolidone. Colloid Polym Sci 1965;203:4-9.
Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48-9.
Bugay DE. Characterization of the solid-state: Spectroscopic techniques. Adv Drug Deliv Rev 2001;48:43-65.
Cilurzo F, Minghetti P, Casiraghi A, Montanari L. Characterization of nifedipine solid dispersions. Int J Pharm 2002;242:313-7.
Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 1997;86:1-2.
Muralidar S, Devala G, Rajesh B, Karunakar R, Nikhat SR. Fast dissolving of celecoxib tablet containing solid dispersion of celecoxib. Int J Pharm Sci Res 2010;9:34-40.
Sathali AH, Prakash T. Formulation and evaluation of fast dissolving tablets of lamivudine. Int J Pharm Biol Res 2012;5:98-112.
Kakade SM, Mannur VS, Ramani KB, Dhada AA, Naval CV, Bhagwat A. Formulation and evaluation of mouth dissolving tablets of losartan potassium by direct compression techniques. Int J Pharm Sci Res 2010;1:290-5.
Tiwary V, Kinikar DJ, Pillai K, Gokulan PD. Preparation and evaluation of fast dissolving tablets of celecoxib. J Curr Pharm Res 2010;4:4-11.
Ford JL. The current status of solid dispersions. Pharm Acta Helv 1986;61:69-88.
Hawi A, Bell G. Preformulation studies of NVP, a reverse transcriptase inhibitor. Pharm Res 1994;11:S236-40.
Wacher VJ, Wong S, Wong HT. Peppermint oil enhances cyclosporine oral bioavailability in rats: Comparison with D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole. J Pharm Sci 2002;91:77-90.
Kawtikwar PS, Zade PS, Karkar M. Formulation, evaluation and optimization of fast dissolving tablet containing tizanidine HCl. Int J Pharm Tech Res 2009;1:34-42.
Altaf AS, Sivakranth M, Rajasekhar S. Formulation and evaluation of oral fast dissolving tablets of sildenafil citrate. Int J Pharm Sci 2011;3:112-21.
Khole SR, Chaudhari PD, More DM. Development and evaluation of melt in mouth tablets of rizatriptan benzoate by sublimation technique. Int J Pharm Sci Res 2011;2:839-48.
Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of valsartan. Int J Pharm Sci 2009;1:219-26.
Rampure MV, Raju SA, Shirsand SB, Swamy PV, Nagendrakumar D, Basawaraj B, et al. Formulation and evaluation of orodispersible tablets of alfuzosin. Int J Pharm Tech Res 2010;2:84-8.
Chander H, Kumar S, Bhatt B. Formulation and evaluation of fast dissolving tablets of ramipril. Der Pham Sin 2011;2:153-60.
Narayana PK, Kumari SK, Narasu L. Solubility and dissolution rate determination of different antiretroviral drugs in different pH media using UV visible spectrophotometer. Eur J Chem 2008;5:1159-64.
Merchant HA, Shoaib HM, Tazeen J, Yousuf RI. Once-daily tablet formulation and in vitro release evaluation of cefpodoxime using hydroxypropyl methylcellulose: A technical note. AAPS Pharm Sci Tech 2006;7:E178-83.
Mu L, Feng SS. Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel (Taxol). J Control Release 2002;80:129-44.
Gujjar PP, Kokil AA, Gaurav YA. Improvement in physicochemical properties of NVP co-crystals. Int J Pharm Technol 2012;4:4831-42.
Repka MA, McGinity JW. Influence of vitamin E TPGS on the properties of hydrophilic films produced by hot-melt extrusion. Int J Pharm 2000;202:63-70.
Sarkar M, Perumal OP, Panchagnula R. Solid-state characterization of nevirapine. Indian J Pharm Sci 2008;70:619-30.
Xie Y, Li G, Yuan X, Cai Z, Rong R. Preparation and in vitro evaluation of solid dispersions of total flavones of Hippophae rhamnoides L. AAPS Pharm Sci Tech 2009;10:631-40.
Ruan LP, Yu BY, Fu GM, Zhu DN. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal 2005;38:457-64.
Sharma D. Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate for respiratory disorders. ISRM Pharm 2013;12:31-40.
Basu B, Bagadiya A, Makwana S, Vipul V, Batt D, Dharamsi A, et al. Formulation and evaluation of fast dissolving tablets of cinnarizine using superdisintegrant blends and subliming material. J Adv Pharm Technol Res 2011;2:266-73.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
