FORMULATION AND EVALUATION OF DOLUTEGRAVIR SODIUM SOLID DISPERSIONS AND FAST DISSOLVING TABLETS USING POLOXAMER-188 AND JACK FRUIT SEED STARCH AS EXCIPIENTS

Sundeep Mupparaju Sundeep Mupparaju,Sandeep Doppalapudi Sandeep Doppalapudi,Vidyadhara Suryadevara Vidyadhara Suryadevara,Ramu Anne Ramu Anne,Sasidhar Reddyvallam Lc Sasidhar Reddyvallam Lc,Sailaja Yallam Sailaja Yallam

doi:10.22159/ajpcr.2019.v12i6.33302

Sundeep Mupparaju Sundeep Mupparaju, Sandeep Doppalapudi Sandeep Doppalapudi + Show 4 more

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https://doi.org/10.22159/ajpcr.2019.v12i6.33302

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Abstract

Objective: The current work mainly focuses on solubility enhancement of dolutegravir which is a biopharmaceutical classification system Class-II drug using jack fruit seed starch (JFS2) as excipient which improves the drug release. Materials and Methods: Starches were extracted using aqueous and alkali methods (sodium hydroxide at 0.1%, 0.25%, and 0.5% concentrations) from jack fruit seed powder. These starches were evaluated for phytochemical and physicochemical parameters. Fast dissolving tablets were prepared using dolutegravir sodium solid dispersion, JFS2, and croscarmellose sodium (CCS) in various concentrations using wet granulation technique. Various pre- and post-compression parameters were evaluated along with in vitro drug release studies; characterization studies such as Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction (XRD), and stability studies. Results: Phytochemical tests revealed the presence of only starch in all extracts. Starch prepared from 0.1% sodium hydroxide (JFS2) showed best physicochemical properties. From in vitro dissolution studies, it was observed that solid dispersion formulation DF3 containing dolutegravir sodium and poloxamer-188 in 1:1.5 ratios showed a better dissolution rate. From in vitro dissolution studies, tablet formulations DFT6 and DFT9 containing 12.5% w/w of JFS2 and 12.5% w/w of CCS showed enhanced dissolution rate compared with other formulations. FTIR and DSC studies revealed that there were no major interactions between drug and excipients. XRD studies revealed the nature of formulations. Accelerated stability studies showed that all tablets were stable. Conclusion: The tablets prepared using jack fruit starch seed starch revealed the superdisintegrant property of starch.

Highlights

Solubility is an important physicochemical factor affecting the absorption of the drug and its therapeutic effectiveness
From in vitro dissolution studies, it was observed that solid dispersion formulation DF3 containing dolutegravir sodium and poloxamer-188 in 1:1.5 ratios showed a better dissolution rate
From in vitro dissolution studies, tablet formulations DFT6 and DFT9 containing 12.5% w/w of JFS2 and 12.5% w/w of croscarmellose sodium (CCS) showed enhanced dissolution rate compared with other formulations

Summary

Introduction

Solubility is an important physicochemical factor affecting the absorption of the drug and its therapeutic effectiveness. Scientists are focusing on the development of oral dosage forms of poor aqueous solubility drugs through various solubility enhancing approaches. Among these approaches, preparation of solid dispersions is one of the widely used approaches. Fast dissolving tablet is a solid dosage form containing a medicinal substance or active ingredient which disintegrates rapidly usually within a matter of seconds when placed on the tongue. It helps in faster drug release and better effect of formulation. Several synthetic carriers have been developed, natural carrier development is gaining focus in recent days due to their easy availability [6]

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