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

The 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 showed crystalline morphology. The solid state analysis undertaken by using differential scanning calorimetry and hot stage microscopy confirmed that SCS are in crystalline state. Similarly, X-ray powder diffraction analysis revealed that pure drug, crystalline carriers and developed SCS are in crystalline state. 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 of the FTIR imaging. 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

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

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

Kinetic energy and scalar spectra in high Rayleigh number axially homogeneous buoyancy driven turbulence

Kinetic energy and scalar spectra from the measurements in high Rayleigh number axially homogeneous buoyancy driven turbulent flow are presented. Kinetic energy and concentration (scalar) spectra are obtained from the experiments wherein density difference is created using brine and fresh water and temperature spectra are obtained from the experiments in which heat is used. Scaling of the frequency spectra of lateral and longitudinal velocity near the tube axis is closer to the Kolmogorov-Obukhov scaling, while the scalar spectra show some evidence of dual scaling, Bolgiano-Obukhov scaling followed by Obukhov-Corrsin scaling. These scalings are also observed in the corresponding second order spatial structure functions of velocity and concentration fluctuations. Published by AIP Publishing

Intensity and angle-of-arrival spectra of laser light propagating through axially homogeneous buoyancy-driven turbulence

Frequency spectra obtained from the measurements of light intensity and angle of arrival (AOA) of parallel laser light propagating through the axially homogeneous, axisymmetric buoyancy-driven turbulent flow at high Rayleigh numbers in a long (length-to-diameter ratio of about 10) vertical tube are reported. The flow is driven by an unstable density difference created across the tube ends using brine and fresh water. The highest Rayleigh number is about 8 x 10(9). The aim of the present work is to find whether the conventional Obukhov-Corrsin scaling or Bolgiano-Obukhov (BO) scaling is obtained for the intensity and AOA spectra in the case of light propagation in a buoyancy-driven turbulent medium. Theoretical relations for the frequency spectra of log amplitude and AOA fluctuations developed for homogeneous isotropic turbulent media are modified for the buoyancy-driven flow in the present case to obtain the asymptotic scalings for the high and low frequency ranges. For low frequencies, the spectra of intensity and vertical AOA fluctuations obtained from measurements follow BO scaling, while scaling for the spectra of horizontal AOA fluctuations shows a small departure from BO scaling. (C) 2016 Optical Society of Americ

Two regimes of flux scaling in axially homogeneous turbulent convection in vertical tube

From experiments of axially homogeneous turbulent convection in a vertical tube using heat (Prandtl number Pr 6 ) and brine (Pr 600 ) we show that at sufficiently high Rayleigh numbers (Ra-g), the Nusselt number Nu(g) similar to (RagPr)(1/2), which corresponds to the so-called ultimate regime scaling. In heat experiments below certain Rag,however,there is transition to a new regime, Nu(g) similar to (RagPr)(0.3). This transition also seems to exist in earlier reported data for Pr = 1 and Pr 600 , at different Ra-g. However, the transition occurs at a single Grashof number, Gr(gc) 1.6 x10(5) , and unified flux scalings for Pr >= 1 , Nug/Pr similar to Gr(g)(0.3), and Nu(g)/Pr similar to Gr(g)(1/2) can be given for the two regimes

Exploring the potential of porous silicas as a carrier system for dissolution rate enhancement of artemether

AbstractMalaria is a parasitic and vector determined blood-conceived infectious disease transmitted through infected mosquitoes. Anti-malarial drug resistance is a major health problem, which hinders the control of malaria. A Results of a survey of drug-resistant malaria demonstrated safe proclivity to nearby all anti-malarial regimes accessible except from artemisinin and its derivatives. Artemether is a BCS class IV drug effective against acute and severe falciparum malaria; hence there is a strong need to improve its solubility. Silica is one of the most widely studied excipients. Silica can be used in solubility enhancement by preparing its solid solution/dispersion with the drug. The objective of this research was to improve dissolution rate of Artemether using non-precipitated porous silica (Aeroperl 300 Pharma) and precipitated silica like EXP. 9555, EXP. 9560, and EXP. 9565. Specific surface area calculated from BET method of porous silicas viz. APL 300 (A), Exp. 9555 (B), Exp. 9560 (C), Exp. 9565 (D) was found to be 294.13 m2/g (A), 256.02 m2/g (B), 213.62 m2/g (C) and 207.22 m2/g (D) respectively.The drug release from the developed formulation was found to be significantly higher as compared to neat ARM. This improved solubility and release kinetics of ARM may be attributed to high surface area, improved wettability and decreased crystallinity. Solid-state characterization of the developed optimized formulation F3 was carried out with respect to FTIR chemical imaging, XRD, SEM, and DSC. All the porous silicas which we have explored in the present context showed a significant capability as a carrier for solubility enhancement of ARM

Development of amorphous dispersions of artemether with hydrophilic polymers via spray drying: Physicochemical and in silico studies

Artemether (ARM) is a poorly water soluble and poorly permeable drug effective against acute and severe falciparum malaria, hence there is a strong need to improve its solubility. The objective of the study was to enhance the solubility and dissolution rate of ARM by preparation of solid dispersions using spray-drying technique. Solid dispersions of ARM were prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2, 1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) to identify the physicochemical interaction between drug and carrier, as well as effect on dissolution. The prepared solid dispersion of ARM with polymers showed reduced crystallinity as compared to neat ARM, which was confirmed by DSC and XRD. Drug/polymer interactions were studied in-silico by docking and molecular dynamics which indicated formation of van der Waals type of interactions of ARM with the polymers. Based on solubility studies, the optimum drug/Soluplus ratio was found to be 1:3. The dissolution studies of formulation SD3 showed highest drug release up to 82% compared to neat ARM giving only 20% at 60 minutes. The spray-dried products were free of crystalline ARM; possessed higher dissolution rates, and were stable over a period according to ICH guidelines. These findings suggest that an amorphous solid dispersion of ARM could be a viable option for enhancing the dissolution rate of ARM

Abstracts of Scientifica 2022

This book contains the abstracts of the papers presented at Scientifica 2022, Organized by the Sancheti Institute College of Physiotherapy, Pune, Maharashtra, India, held on 12–13 March 2022. This conference helps bring researchers together across the globe on one platform to help benefit the young researchers. There were six invited talks from different fields of Physiotherapy and seven panel discussions including over thirty speakers across the globe which made the conference interesting due to the diversity of topics covered during the conference. Conference Title:  Scientifica 2022Conference Date: 12–13 March 2022Conference Location: Sancheti Institute College of PhysiotherapyConference Organizer: Sancheti Institute College of Physiotherapy, Pune, Maharashtra, Indi