Effect of melt extrudability and melt binding efficiency of polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer (Soluplus®) on release pattern of hydrophilic and high dose drugs

The present study explores the effect of melt binding of Soluplus® on in vitro release profiles of two hydrophilic drugs, metformin hydrochloride, and paracetamol. The melt viscosities of bulk polymer and physical mixtures with different concentrations of selected APIs were analyzed by using a rheometer. The rheological evaluation revealed both the suitable temperature range for melt extrusion process and drug-polymer extrudability. The effect of formulation and processing parameters (e.g. polymer/drug ratio, temperature, screw speed) on extrudability were evaluated in terms of torque and residence time analysis. The extrudates obtained via hot melt extrusion (HME) processing exhibited good flow and compressibility. Differential scanning calorimetry (DSC) and X-ray diffraction studies examined the change in glass transition temperature (Tg) and crystalline pattern of extruded formulations where all extruded formulations seemed to have retained their crystallinity. The thermogravimetric analysis determined the thermal stability (weight loss) as a function of operating temperature whereas scanning electron microscopy (SEM) showed agglomerated microstructure and rough surface with a porous network and void spaces. The tablets obtained after compression of milled extrudates showed excellent hardness with robust tablet characteristics. The in vitro release studies of individual batches performed in various USP recommended dissolution media (for paracetamol) showed the pH-independent release of the hydrophilic drugs from the polymer matrices

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

Extraction of rutin from tagetes erecta (Marigold) and preparation of peroral nano-suspension for effective antitussive/expectorant therapy

The present study narrates the extraction of rutin from Tagetes erecta (Marigold) via maceration followed by ultrasonication. The extracted rutin was further fabricated into nanoparticles by high-pressure homogenization (HPH) and assessed by HPLC, DSC, XRD, TEM, and FTIR spectroscopy. The optimized batch of nanoparticles obtained using 32 central composite design (CCD) which exhibited particle size 209±14 nm, PDI 0.234±0.06, and 92±1.3% entrapment efficiency. The lyophilized rutin nanoparticles were further converted into nano-suspension. Interestingly, the rutin nano-suspension exhibited a similar antitussive effect in vivo as that by standard treatment pentoxyverine and reduced the coughing times within 2 min. Also, the phlegm showed high UV absorbance, implying its better expectorant activity than the standard and control. The rutin nano-suspension was highly stable and shelf life was found to be ∼29.1 months. The present study, for the first time, paves a way for the use of rutin nano-suspension to overcome chest congestion, shortening of breath, and in the management of cough