Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization.

Rabia Munir,Nayyer Islam,Ahmed Khames,Salah-Ud-Din Khan,Sajid Asghar,Pervaiz Akhtar Shah,Abdul Hadi,Ikram Ullah Khan,Memoona Ishtiaq,Haroon Khalid Syed,Muhammad Irfan,Muhammad Shahid Iqbal,Mohammad A S Abourehab,Misbah Hameed,Sana Inam,Shahzadi Filza Hassan

doi:10.3390/polym14030579

Abstract

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

Highlights

To design safe and effective dosage form, drug solubility is the most important parameter among all others
This study revealed that, in the case of the binary inclusion complex, the increase in the polymer (HPβCD) concentration contributed to the comparative increase in drug solubility [18,34]
An indication of the process of transfer of DEX from water to the aqueous solution of HPβCD was obtained from the values of Gibbs free-energy change

Summary

Introduction

To design safe and effective dosage form, drug solubility is the most important parameter among all others. To address the limitations of BCS Class II drugs, several methods have been developed, including salt formation, lipid-based formulations, particle size reduction, solid dispersions, complexation with cyclodextrins or its derivatives [5,6,7,8,9] and supercritical antisolvent co-precipitation [10]. Cyclodextrins (CDs) inclusion complexation is one of the several methods available for improving the solubility of drug molecules. Inclusion complexation may enhance the bioavailability and efficacy of the drugs, and this may reduce the dose frequency [9,10,11]. The amorphous structure of HPβCD is significant in reducing polymorphic transition and crystallization of poor water-soluble drugs, enhancing the drug solubility and oral bioavailability

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Results

Conclusion