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Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology

Abstract

The current study investigates the dissolution rate performance of amorphous solid solutions of a poorly water-soluble drug, efavirenz (EFV), in amorphous Soluplus® (SOL) and Kollidon® VA 64 (KVA64) polymeric systems. For the purpose of the study, various formulations with varying drug loadings of 30, 50, and 70% w/w were developed via hot-melt extrusion processing and adopting a Box–Behnken design of experiment (DoE) approach. The polymers were selected based on the Hansen solubility parameter calculation and the prediction of the possible drug-polymer miscibility. In DoE experiments, a Box–Behnken factorial design was conducted to evaluate the effect of independent variables such as Soluplus® ratio (A1), HME screw speed (A2), and processing temperature (A3), and Kollidon®VA64 ratio (B1), screw speed (B2), and processing temperature (B3) on responses such as solubility (X1 and Y1) and dissolution rate (X2 and Y2) for both ASS [EFV:SOL] and BSS [EFV:KVA64] systems. DSC and XRD data confirmed that bulk crystalline EFV transformed to amorphous form during the HME processing. Advanced chemical analyses conducted via 2D COSY NMR, FTIR chemical imaging, AFM analysis, and FTIR showed that EFV was homogenously dispersed in the respective polymer matrices. The maximum solubility and dissolution rate was observed in formulations containing 30% EFV with both SOL and KVA64 alone. This could be attributed to the maximum drug-polymer miscibility in the optimized formulations. The actual and predicted values of both responses were found precise and close to each other.

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Abbreviations

EFV:

Efavirenz

SS:

Solid solution

HME:

Hot-melt extrusion

SOL:

Soluplus

KVA64:

Kollidon® VA64

BBD:

Box–Behnken design

SL:

Sodium lauryl sulfate

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Acknowledgments

The authors would like to acknowledge Laurus Labs, Hyderabad, India, for the genuine gift sample of efavirenz. The author is thankful to Dr. Rahul Aware and Vasant Shetty from ACG Machines Pvt., Ltd., for allowing their twin-screw HME facility at Pune, India. The authors are thankful to University Grants Commission India for providing the research fellowship. The authors are thankful to S.A.I.F., Department at Indian Institute of Technology, Mumbai, for FTIR imaging analysis and 2D COSY analysis of the samples.

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Correspondence to Jaywant Pawar.

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Pawar, J., Suryawanshi, D., Moravkar, K. et al. Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology. Drug Deliv. and Transl. Res. 8, 1644–1657 (2018). https://doi.org/10.1007/s13346-018-0481-0

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  • DOI: https://doi.org/10.1007/s13346-018-0481-0

Keywords

  • Box–Behnken design
  • Hot-melt extrusion
  • Efavirenz
  • Solubility enhancement
  • 2D COSY NMR