Hot melt extrusion based solid solution approach: Exploring polymer comparison, physicochemical characterization and in-vivo evaluation

Fule, Ritesh; Paithankar, Vivek; Amin, Purnima D.

doi:10.1016/j.ijpharm.2015.12.062

Cited by 31 publications

(28 citation statements)

References 31 publications

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“…Moreover, all characteristics drug peak frequencies were observed in SS formulation that confirms the stable structural and physico-chemical state of EFV in all formulations [13].…”

Section: D Cosy Nmr Analysissupporting

confidence: 67%

“…If solubility parameter difference is less than 7 MPa 1/2 , itis generally accepted as an indication of miscibility whereas for a difference of more than 10 MPa 1/2 the system is likely to be immiscible. The underlying concept of the foregoing claim is based on the prediction that the energy of mixing required for the intermolecular interaction between a drug and polymer will be balanced by the [13],respectively. This indicates that the the difference in the solubility parameters (δ) value in EFV/SOL and EFV/KVA64 systems as 4.95 and 5.12, respectively, which outlines the possibility of the formation of miscible systems, hence were proceeded further with the HME processing.…”

Section: Polymer Selection For Efv Ss Formulationmentioning

confidence: 99%

“…We are reporting preparation of EFV solid solutions by HME technology using two widely used thermostable amorphous polymers; Soluplus® (SOL) (polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer) and Kollidon® VA64 (KVA64) (Vinylpyrrolidone-vinyl acetate copolymer) by adopting a Quality by Design (QbD) approach. Both polymers are amphiphilic in nature that can work as solubilizing agent and have been reported in the literature for dissolution enhancement of other poorly water soluble drugs [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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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

Pawar

Suryawanshi

Moravkar

et al. 2018

Drug Deliv. and Transl. Res.

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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 (A), HME screw speed (A), and processing temperature (A), and Kollidon®VA64 ratio (B), screw speed (B), and processing temperature (B) on responses such as solubility (X and Y) and dissolution rate (X and Y) 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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“…Moreover, all characteristics drug peak frequencies were observed in SS formulation that confirms the stable structural and physico-chemical state of EFV in all formulations [13].…”

Section: D Cosy Nmr Analysissupporting

confidence: 67%

Section: Polymer Selection For Efv Ss Formulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Pawar

Suryawanshi

Moravkar

et al. 2018

Drug Deliv. and Transl. Res.

Self Cite

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show abstract

“…In addition, the FT‐IR spectra indicated the generation of hydrogen bonds during the preparation of the FF solid dispersion by HME technology (Vo et al., ). Although a previous FT‐IR study reported that an HME‐based solid solution of artesunate in the water‐soluble Soluplus ® and Kollidon ® VA64 polymers did not exhibit any changes in molecular stretching (although slight shifts of specific peaks were observed), the resulting molecular dispersions significantly improved the dissolution properties of artesunate (Fule, Paithankar, & Amin, ). The absence, shift, and decreased intensity of the characteristic peaks are actually related to the phase and groups of the drug and supplementary materials.…”

Section: Discussionmentioning

confidence: 94%

Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

Wen

Feng

et al. 2018

Vet Pharm & Therapeutics

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The objective of this work was to manufacture an enteric formulation of florfenicol (FF) using hot-melt extrusion (HME) technology and to evaluate its in vitro dissolution and in vivo pharmacokinetics. For the HME process, hypromellose acetate succinate LG (HPMCAS-LG) was the enteric polymer mixed with FF, and the two components were extruded with a standard screw configuration at a speed of 50 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT-IR) were performed to characterize the HME extrudate. The release percentage of the enteric formulation in the acidic stage was <10% of the loaded FF, whereas that in the phosphate buffer stage was >80%. Pharmacokinetic evaluations in swine revealed that the enteric formulation had a longer t and MRT than commercially available FF powder (FULAIKA ), indicating that the novel formulation exhibited enteric and sustained release properties. Compared with the commercial product, the relative bioavailability of the enteric formulation reached up to 117.2%. This study suggests that this formulation may have potential for future commercialization.

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“…Thus, we choose polyols such as xylitol and pearlitol as hydrophilic crystalline carriers for solubility enhancement of EFV. Solubility parameters usually used to access mixing capability between polymers and drugs as reported in literature (Fule et al, 2016;Lu et al, 2015). Based on the group contribution method calculation solubility parameters of EFV, pearlitol (mannitol) and xylitol are 24.55 MPa 1/2 (Sathigari et al, 2012), 40.5 MPa 1/2 (Thommes et al, 2011), and 36.86 MPa 1/2 (Kitak et al, 2015), respectively.…”

Section: Selection Of Polyols As Carrier For Hmementioning

confidence: 99%

Solid crystal suspension of Efavirenz using hot melt extrusion: Exploring the role of crystalline polyols in improving solubility and dissolution rate

Pawar

Fule

Maniruzzaman

et al. 2017

Materials Science and Engineering: C

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Poor aqueous solubility of drugs has emerged as a major issue for pharmaceutical scientists from many decades. The current study explores the manufacture and development of a thermodynamically stabilized solid crystal suspension (SCS) of poorly water soluble drug efavirenz via hot melt extrusion. Efavirenz is a non-nucleoside reverse transcriptase inhibitor and belongs to BCS class II. The SCS was prepared using pearlitol and xylitol as a crystalline carrier. The drug-excipient blend was processed by hot melt extrusion with up to 50% (w/w) drug loading. Physico-chemical characterization of the SCS conducted via a scanning electron microscopy, differential scanning calorimetry and hot stage microscopy confirmed that SCS are in crystalline state. Similarly, X-ray powder diffraction analysis revealed highly crystalline existence of pure drug, crystalline carriers and developed SCS. The FTIR chemical imaging analysis of SCS formulations showed a homogeneous drug distribution within respective crystalline carriers while an advanced chemical analysis via atomic force microscopy and Raman analysis complemented the foregoing findings. The developed SCS1 formulation showed up to 81 fold increase in the solubility and 4.1 fold increase in the dissolution rate of the drug compared to that of the bulk substance. Surprisingly, the developed SCS formulation remained stable for a period of more than one year at accelerated conditions inferred from dissolution studies. It can be concluded that the SCS approach can be used as an alternative contemporary technique to enhance the dissolution rates of many other poorly water-soluble drugs by means of thermal HME processing.

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Hot melt extrusion based solid solution approach: Exploring polymer comparison, physicochemical characterization and in-vivo evaluation

Cited by 31 publications

References 31 publications

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

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

Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

Solid crystal suspension of Efavirenz using hot melt extrusion: Exploring the role of crystalline polyols in improving solubility and dissolution rate

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