• RAHUL RADKE Faculty of Pharmacy, Oriental University, Indore, M.P. India
  • NEETESH K. JAIN Faculty of Pharmacy, Oriental University, Indore, M.P. India




Ambrisentan, Gelucire 50/13, Bioavailability, Solid dispersion, Kneading technique


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 formulation showed increase in drug solubility and dissolution, when compared with its pure form. Aqueous solubility of drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of 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 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 griseofluvin. Int J Pharm 2004; 269(2): 443-450.

Singh G, Kaur I, Gupta D, Sharma S. Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review. Indian J Pharm Sci. 2017;79(5): 674-687.

Aulton ME, Pharmaceutics: The science of dosage form design, 1st ed, London: Churchill Livingstone, 1996.

Vo CL, Park C, Lee B. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. European Journal of Pharmaceutics and Biopharmaceutics. 2013; 85(3):799-813.

Sareen S, Mathew G, Joseph L. Improvement in solubility of poor water-soluble drugs by solid dispersion. International Journal of Pharmaceutical Investigation 2012; 2(1): 12-17.

Raymond CR, Paul JS, Marian EQ. Handbook of Pharmaceutical Excipients. 6th edition, Pharmaceutical Press; 557-560.

Yu DG, Yang GM, White CB, Lu P, Zhang L, Zhu LM. Third generation solid dispersions of ferulic acid in electrospun composite nanofibers. International Journal of Pharmaceutics 2010; 400:158–164.

European medicine agency; Evaluation of medicines for human use, Assesment reportfor volibris Doc. Ref.:EMEA/123999/2008. P.N.1-44.

Barst RJ. A review of pulmonary arterial hypertension: role of ambrisentan. Vasc Health Risk Manag 2007;3(1):11.

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.

Modi A, Tayade P. Enhancement of Dissolution Profile by solid dispersion (Kneading) Technique. AAPS PharmSciTech 2006; 7(3):68-73.

Iqbal A, Hossain MS, Shamim MA, Islam M, Siddique MAT. Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion. Tropical Journal of Pharmaceutical Research 2020; 19(6): 1131-1138.

Sathali AAH, Jayalakshmi J. Enhancement of solubility and dissolution rate of olmesartan medoxomil by solid dispersion technique. J. Curr. Chem. Pharm. Sc. 2013: 3(2):123-134.

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. Pharm. 2014; 3(6): 427-431.

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.

Adahalli SB, Tallur M. Formulation And Evaluation of Tablet Prepared By Co-amorphous System Containing Anti-Hypertensive And Anti-Hyperlipidemic Drug. Int J Pharm Pharm Sci, 2016; 8(9): 182-193.

Varma MM, Razia Begum SK. Formulation, Physicochemical Evaluation and Dissolution Studies of Carbamazepine solid dispersions. International Journal of Pharmaceutical Sciences. 2012; 5(3):1790-1807.

Avachat A, Raut V. Solubility and dissolution enhancement of Nebivolol hydrochloride using hydrophilic carriers. Asian Journal of Pharmaceutical Sciences. 2012;7(5):337-345.

Deshmane S, Deshmane S, Shelke S, Biyani K. Enhancement of solubility and bioavalibability of Ambresentan 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):1001-1011.

Srinivas I, Bhikshapathi DVRN. Preparation and in vivo Evaluation of Solid Dispersions Using Repaglinide. International Journal of Pharmaceutical Sciences and Drug Research. 2018; 10(5): 362-371.

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 Research International. 2014 : 1-10.

Maulvi FA, Dalwadi SJ, Thakkar VT, Soni TG, Gohel MC, Gandhi TR. Improvement of dissolution rate of aceclofenac by solid dispersion technique. Powder Technol. 2014; 207 :47–54.

Daravath B., Tadikonda RR, Vemula SK. Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen. Drug Dev Ind Pharm, Early Online: 1-9.

Mehanna MM, Motawaa AM, Samaha MW. In sight into tadalafil-block copolymerbinary solid dispersion: Mechanistic investigation of dissolution enhancement.

International Journal of Pharmaceutics. 2010; 402 (1-2):78-88.

Babu GVMM, Prasad CDS, Murthy KVR. Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water soluble drug nimodipine. Int. J. Pharm. 2002; 234:1-17.

Deshkar S, Satpute A. Formulation and Optimization of Curcumin Solid Dispersion Pellets for Improved Solubility. Int J App Pharm. 2020; 12(2): 36-46.

Ghareeb MM, Abdulrasool AA, Hussein AA, Noordin MI. Kneading Technique for Preparation of Binary Solid Dispersion of Meloxicam with Poloxamer 188. AAPS PharmSciTech, 2009, 10(4), 1206-1215.

Chen L, Junhua W, Bin S, Yuanxing Z, Tiankun G, Yuanying P. Enhancing theBioavailability of Cyclosporine A Using Solid Dispersion Containing Polyoxyethylene (40) Stearate. Drug Dev Ind Pharm. 2006; 32:115-123.

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; 8:110-118.



How to Cite

RADKE, R., & K. JAIN, N. (2021). ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS. International Journal of Applied Pharmaceutics, 14(1). https://doi.org/10.22159/ijap.2022v14i1.43347



Original Article(s)