IN VITRO-IN VIVO EVALUATION OF FAST-DISSOLVING TABLETS CONTAINING SOLID DISPERSION OF OXCARBAZEPINE
Keywords:
Dissolution profile, Hydrophilic carrier, Melting method, Solubility, Solid dispersionAbstract
Objective: Investigation of in vitro/in vivo behaviour of fast-dissolving tablets containing solid dispersions of oxcarbazepine is the focus of the present research work.
Methods: The effect of various hydrophilic polymers on the aqueous solubility of oxcarbazepine was studied. Polyethylene glycol 6000 carrier was selected and solid dispersions were prepared by various methods. A total of nine formulations were compressed into fast-dissolving tablets using avicel PH 102 as a directly compressible filler and ac-di-sol, sodium starch glycolate and crospovidone as super disintegrants and evaluated for pre and post compression parameters and in vitro drug release. In vivo studies of the pure drug, optimized formulation and marketed formulation were carried out on male Wistar rats and pharmacokinetic parameters were calculated using the pk function for Microsoft excel.
Results: Mathematical analysis of in vitro data suggested that the first order was the most suitable mathematical model for describing the optimized formulation. The first-order plot was found to be fairly linear for optimized formulation as indicated by its high regression value. Stability studies indicated that the effect of storage was insignificant at 5% level of confidence. The optimized formulation has shown Tmax of 0.5 h, which was highly significant (P<0.05) when compared with pure drug and marketed formulation.
Conclusion: Therefore, the solid dispersions prepared by melting method using polyethylene glycol 6000 as hydrophilic carrier can be successfully used for the improvement of dissolution of oxcarbazepine and resulted in faster onset of action as indicated by in vitro and in vivo studies.
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References
O’Neil MJ. Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals. 13th Ed. Whitehouse Station. NJ Merck. Co., Inc; 2001.
Murray L. Physician's Desk Reference. 56th Ed. Thomson Health Care; 2002. p. 2407.
Srinarong P, Kouwen S, Visser MR, Hinrichs WL, Frijlink HW. Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets. Pharm Dev Technol 2010;15:460-8.
Yin LF, Huang SJ, Zhu CL, Zhang SH, Zhang Q, Chen XJ. In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier. Drug Dev Ind Pharm 2012;38:1371-80.
Shreya Shah, Sachi Joshi, Lin S, Madan PL. Preparation and characterization of spironolactone solid dispersions using hydrophilic carriers. Asian J Pharm Sci 2010;7:40-9.
Shah J, Vasanti S, Anroop B, Vyas H. Enhancement of dissolution rate of valdecoxib by solid dispersion technique with PVP K 30 and PEG 4000: preparation and in vitro evaluation. J Incl Phenom Macrocycl Chem 2009;63:69–75.
Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instrum 1965;4:117–212.
Chanda R, Kapoor VK, Kumar A. Analytical techniques used to characterize drug-polyvinyl-pyrrolidone systems in solid and liquid states-an overview. J Sci Ind Res 2006;65:459–69.
Ghareeb MM, Abdulrasool AA, Hussein AA, Noordin MI. Kneading technique for preparation of binary solid dispersion of meloxicam with poloxamer 188. AAPS PharmSciTech 2009;10:1206–15.
Patil MP, Gaikwad NJ. Preparation and characterization of gliclazide-polyethylene glycol 4000 solid dispersions. Acta Pharm 2009;59:57-65.
Md Armin Minhaz, Md Mofizur Rahman, Md Qamnul Ahsan, Abul Bashar Ripon Khalipha, Mohammed Raihan Chowdhury. Dissolution enhancement of poorly soluble drug by solvent evaporation method using hydrophilic polymer: a solid dispersion technique. Int J Pharm Life Sci 2012;1:1-18.
Malke Sheetal, Shindhaye Supriya, Kadam VJ. Formulation and evaluation of oxcarbazepine fast dissolving tablets. J Pharm Sci 2007;69:211-4.
Zade PS, Kawtikwar PS, Sakarkar DM. Formulation, evaluation and optimization of fast dissolving tablets containing tizanidine hydrochloride. Int J PharmTech Res 2009;1:34-42.
Gnanaprakash K, Mallikarjuna Rao K, Chandra Sekhar KB, Kadhusudhana Chetty, Alagusundaram M, Ramkanth S. Formulation and evaluation of fast dissolving tablets of valdecoxib. Int J PharmTech Res 2009;1:1387-93.
Suhas M Kakade, Vinodh S Mannur, Ketan B Ramani, Ayaz A Dhada, Chirag V Naval. Formulation and evaluation of mouth dissolving tablets of losartan potassium by direct compression techniques. Int J Res Pharm Sci 2010;3:290-5.
Prashant Khemariya, Kavita R Gajbhiye, Vikas Deep Vaidya, Rajesh Singh Jadon, Sachin Mishra. Preparation and evaluation of mouth dissolving tablets of meloxicam. Int J Drug Delivery 2010;2:76-80.
Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of valsartan by direct compression. Int J Pharm Pharm Sci 2009;1:219-26.
Mohan A, Ghosh SK. New method for spectrophotometric estimation of new antiepileptic drugs in solid dosage forms. Asian J Res Chem 2009;2:322-5.
Pushpendra kumar Pasupathi, Margret Chandira, Debjit Bhowmik, Chiranjib Jayakar. Formulation and evaluation of fast dissolving tablets of rupatadine fumarate. Der Pharm Lett 2009;1:151-63.
Kamal Dua, Kavita Pabreja, Ramana MV, Vinny Lather. Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac. J Pharm BioAllied Sci 2011;3:417–25.
Avachat A, Kotwal V. Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondroitin sulphate. AAPS PharmSciTech 2007;8:E1–6.
Mater KM, Nicholls PJ, AL-Hassan MI, Tekle A. Rapid micro method for simultaneous measurement of oxcarbazepine and its active metabolite in plasma by highâ€performance liquid chromatography. J Clin Pharm Ther 1995;20:229-34.
Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother 2010;1:87–93.
Pandit V, Pai RS, Yadav V, Devi K, Surekha BB, Inamdar MN. Pharmacokinetic and pharmacodynamic evaluation of floating microspheres of metformin hydrochloride. Drug Dev Ind Pharm 2013;39:117–27.
Mathews BR. Regulatory aspects of stability testing in Europe. Drug Dev Ind Pharm 1999;25:831–56.
Anupama Kalia, Shelly Khurana, Neena Bedi. Formulation and evaluation of mouth dissolving tablets of oxcarbazepine. Int J Pharm 2009;1 Suppl 1:12-23.
Karthik Neduri, Vijaya Kumar Bontha, Sateesh Kumar Vemula. Different techniques to enhance the dissolution rate of lovastatin: formulation and evaluation. Asian J Pharm Clin Res 2013;6:56-60.
Krishnamurthy A Kamalapurkar, Mahesh P Chitali, Revansidh R Pujari. Formulation development and characterization of fast dissolving tablets of oxcarbazepine. Indian J Pharm Biol Res 2015;3:11-7.