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Abstract

PREPARATION AND CHARACTERIZATION OF POLAXAMER BASED SOLID DISPERSION FOR EFFECTIVE ENHANCEMENT OF SOLUBILITY OF POORLY WATER SOLUBLE DRUG

Raviraj Baghel*, Manish Sharma, Shivam Saxena, Rahul Maurya, Deepti Jain

School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal

ABSTRACT

Poorly soluble drugs represent a problem for their scarce availability related to their low dissolution rate. The major drawback of low aqueous solubility is delays its absorption from the gastrointestinal tract.Solubility behavior of a drug is one of the key determinants of its oral bioavailability.Celecoxib is a highly poorly water-soluble nonsteroidal anti-inflammatory drug (NSAID) with relatively low bioavailability,able to selectively inhibit cyclooxygenase-2 (COX-2).The aim of the present study was to enhance the solubility and dissolution rate of Poorly water soluble by a solid dispersion method using various hydrophilic carriers such as poloxamer 407, PVP, HPMC and PEG were screened. Poloxamer 407was most effective to form a superior solid dispersion of celecoxib having significantly enhanced solubility. Particularly, solid dispersion of celecoxib with poloxamer 407 in the weight ratio of 1:4 prepared by melting solvent method enhanced the solubility of celecoxib to the greatest extent. Poloxamer 407 based solid dispersion showed 65 times higher (0.513 mg/ml) solubility then pure celecoxib whereas solid dispersion of celecoxib with PVP, HPMC and PEG were showed 31 times (0.248mg/ml), 38 times (0.304mg/ml) and 23.5 times (0.182mg/ml) higher solubility than pure celecoxib, respectively However, it exhibited poor physical stability and due to hygroscopic nature of poloxamer 407, solid dispersion showed 10% drug degradation on 45days storage. To avoid this unstable form of poloxamer based solid dispersion, HPMC, PEG-8000, PVP-K30 and their combination were incorporated as an adsorbent of hygroscopic nature and inhibitor the recrystallization of drug. The solid dispersion of celecoxib was characterized by FT-IR, SEM (scanning electron microscopy), (DSC) differential scanning calorimetery, drug content, and in-vitro dissolution profile. The significant enhancement in aqueous solubility of celecoxib achieved by solid dispersion technique opens up the possibility of development of oral dosage form with improved bioavailability employing the technique.

Keywords: Solid dispersion, Celecoxib, Polaxamer, Solubility enhancement, HPMC, PVP.


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