ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS
DOI:
https://doi.org/10.22159/ijap.2022v14i1.43347Keywords:
Ambrisentan, Gelucire 50/13, Bioavailability, Solid dispersion, Kneading technique etcAbstract
Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier.
Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM).
Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations.
Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.
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Naseem A, Olliff CJ, Martini LG, Lloyd AW. Effects of plasma irradiation on the wettability and dissolution of compacts of griseofulvin. Int J Pharm. 2004;269(2):443-50. doi: 10.1016/j.ijpharm.2003.09.029, PMID 14706255.
Singh G, Kaur L, Gupta GD, Sharma S. Enhancement of the solubility of poorly water soluble drugs through solid dispersion: a comprehensive review. Pharm Sci. 2017;79(5):674-87. doi: 10.4172/pharmaceutical-sciences.1000279.
Aulton ME. Pharmaceutics: the science of dosage form design. 1st ed. New York: Churchill Livingstone; 1996.
Vo CL, Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm. 2013;85(3 Pt B):799-813. doi: 10.1016/j.ejpb.2013.09.007, PMID 24056053.
Sareen S, Mathew G, Joseph L. Improvement in solubility of poor water-soluble drugs by solid dispersion. Int J Pharm Investig. 2012;2(1):12-7. doi: 10.4103/2230-973X.96921, PMID 23071955.
Raymond CR, Paul JS, Marian EQ. Handbook of pharmaceutical excipients. 6th ed. Pharmaceutical Press; 2020. p. 557-60.
Yu DG, Yang JM, Branford White CB, Lu P, Zhang L, Zhu LM. Third generation solid dispersions of ferulic acid in electrospun composite nanofibers. Int J Pharm. 2010;400(1-2):158-64. doi: 10.1016/j.ijpharm.2010.08.010, PMID 20713138.
European medicine agency. Evaluation of medicines for human use, Assessment report for volibris Doc. Ref.: EMEA/123999/2008; 2008. p. 1-44.
Barst RJ. A review of pulmonary arterial hypertension: role of ambrisentan. Vasc Health Risk Manag. 2007;3(1):11-22. PMID 17583171.
Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instr. 1965;4:117-212.
Sharma A, Jain CP. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci. 2010;5(1):49-56. PMID 21589768.
Modi A, Tayade P. Enhancement of dissolution profile by solid dispersion (Kneading) technique. AAPS PharmSciTech. 2006;7(3):68. doi: 10.1208/pt070368, PMID 17025249.
Iqbal A, Hossain S, Shamim A, Islam M, Siddique AT. Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion. Trop J Pharm Res. 2020;19(6):1131-8. doi: 10.4314/tjpr.v19i6.2.
Sathali AAH, Jayalakshmi J. Enhancement of solubility and dissolution rate of olmesartan medoxomil by solid dispersion technique. J Curr Chem Pharm Sci 2013;3(2):123-34.
Yunoos M, Lavanya NSL, Sravani G, Madhuri Rao P, Krishna CH. Development of a validated UV spectrophotometric method for the estimation of ambrisentan in pure and marketed formulations. Sch Acad J Pharmacol. 2014;3(6):427-31.
Yang M, Wang P, Huang CY, Ku MS, Liu H, Gogos C. Solid dispersion of acetaminophen and poly (ethylene oxide) prepared by hot-melt mixing. Int J Pharm. 2010;395(1-2):53-61. doi: 10.1016/j.ijpharm.2010.04.033, PMID 20435110.
Adahalli SB, Talluri M. Formulation and evaluation of tablet prepared by coamorphous system containing anti-hypertensive and anti-hyperlipidemic drug. Int J Pharm Pharm Sci. 2016;8(9):182-93. doi: 10.22159/ijpps.2016.v8i9.12895.
Varma MM, SK RB. Formulation, physicochemical evaluation, and dissolution studies of carbamazepine solid dispersions. IJPSN 2012;5(3):1790-807. doi: 10.37285/ijpsn.2012.5.3.7.
Avachat A, Raut V. Solubility and dissolution enhancement of nebivolol hydrochloride using hydrophilic carriers. Asian J Pharm Sci. 2012;7(5):337-45.
Deshmane S, Deshmane S, Shelke S, Biyani K. Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study. Drug Dev Ind Pharm. 2018;44(6):1001-11. doi: 10.1080/03639045.2018.1428339, PMID 29382236.
Srinivas I, Bhikshapathi DVRN. Preparation and in vivo evaluation of solid dispersions using repaglinide. Int J Pharm Sci Drug Res. 2018;10(5):362-71.
Rodde MS, Divase GT, Devkar TB, Tekade AR. Solubility and bioavailability enhancement of poorly aqueous soluble atorvastatin: in vitro, ex vivo, and in vivo studies. BioMed Res Int. 2014;2014:463895. doi: 10.1155/2014/463895, PMID 24995297.
Maulvi FA, Dalwadi SJ, Thakkar VT, Soni TG, Gohel MC, Gandhi TR. Improvement of dissolution rate of aceclofenac by solid dispersion technique. Powder Technol. 2011;207(1-3):47-54. doi: 10.1016/j.powtec.2010.10.009.
Daravath B, Tadikonda RR, Vemula SK. Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen. Drug Dev Ind Pharm. 2015;41(8):1254-62. doi: 10.3109/03639045.2014.940963, PMID 25039470.
Mehanna MM, Motawaa AM, Samaha MW. In: sight into tadalafil-block copolymerbinary solid dispersion: mechanistic investigation of dissolution enhancement. Int J Pharm. 2010;402(1-2):78-88.
Murali Mohan Babu GV, Prasad ChD, Ramana Murthy KV. Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine. Int J Pharm. 2002;234(1-2):1-17. doi: 10.1016/s0378-5173(01)00925-5, PMID 11839433.
Deshkar S, Satpute A. Formulation and optimization of curcumin solid dispersion pellets for improved solubility. Int J Appl Pharm. 2020;12(2):36-46. doi: 10.22159/ijap.2020v12i2.34846.
Ghareeb MM, Abdulrasool AA, Hussein AA, Noordin MI. Kneading technique for preparation of solid binary dispersion of meloxicam with poloxamer 188. AAPS PharmSciTech. 2009;10(4):1206-15. doi: 10.1208/s12249-009-9316-0, PMID 19862626.
Liu C, Wu J, Shi B, Zhang Y, Gao T, Pei Y. Enhancing the bioavailability of cyclosporine a using solid dispersion containing polyoxyethylene (40) stearate. Drug Dev Ind Pharm. 2006;32(1):115-23. doi: 10.1080/03639040500388573, PMID 16455610.
Bhalekar MR, Upadhaya PG, Reddy S, Kshirsagar SJ, Madgulkar AR. Formulation and evaluation of acyclovir nanosuspension for enhancement of oral bioavailability. Asian J Pharm. 2014;8(2):110-8. doi: 10.4103/0973-8398.134942.
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