Solid dispersion

The aim of this study was to prepare and evaluate sublingual fast-disintegrating mucoadhesive tablet (mFDT) containing a poorly soluble drug (carvedilol CAR) to avoid the first pass metabolism and to improve its bioavailability with reduction in dose and also dose related side effects. The tablets were prepared by direct compression method containing solid dispersion of surfactant and drug. The prepared tablets were tested for weight variation, hardness, drug content uniformity, bioadhesive strength and in vitro drug dissolution. The in vitro release of carvedilol was performed under sink conditions (phosphate buffer of pH 6.8, 37±0.5 ºC, 25 rpm) using USP‐XXIV dissolution apparatus. The acceptable in vitro drug release profile was achieved with the formulation F2 which contains the drug and poloxamer in the ratio of 1:2 and superdisintegrant of 3%. The bioadhesive strength of formulation F2 was found to be 13.8 g. The tablets (formulation F2) containing 6.25 mg of carvedilol exhibited > 80 % of drug release within 10 min. FTIR, XRD and DSC studies showed no evidence of interactions between drug, surfactant, and excipients. The tablets apart from fulfilling all official and other specifications, exhibited higher rate of release. The mucoadhesive fast disintegrating drug delivery system of carvedilol for sublingual delivery could be successfully formulated.

Solid dispersion of Oxcarbazepine (OXC) was prepared by hot melt extrusion of OXC with hydrophilic polymer. The main objective was to explore the potential of Hot Melt Extrusion technique (HME) as an industrial scalable green technique for the preparation of solid dispersion and therefore enhancement of dissolution of poorly soluble drug. Polymer for extrusion was selected on the basis of solubility parameters and glass transition (Tg). OXC solid dispersion was prepared using Kollidon VA 64 and Soluplus as hydrophilic carrier. OXC and polymer was mixed in different ratio and extrudates were evaluated for appearance, DSC, PXRD, flow property and dissolution characteristics. DSC and PXRD studies revealed the significant reduction in crystallinity of OXC. OXC-kollidon VA 64 extrudates have good flow property having angle of repose 29° and carr’s index 11.2 and good compressibility with hardness 5-6 kg/cm2. Particle size of extrudates exhibited significant effect on disintegration time and dissolution. OXC release was found to be complete within 45 min from tablets of OXC hot melt extrudates while plain OXC showed just 39 % release. Solid dispersion of OXC was successfully developed using HME technology followed by formulating it into directly compressible tablets.

Domperidone is a water insoluble drug exhibiting poor dissolution pattern. Domperidone is an antiemetic and shows gastroprokinetic properties. It is a weak base and shows poor solubility in alkaline pH. Several methods are being employed to enhance the solubility of domperidone irrespective of its pH dependent solubility. The present protocol aim to design Polyethylene glycol (PEG) based solid dispersions of Domperidone to enhance its solubility. PEG 8000 based solid dispersions containing the drug in different mass ratio i.e. 1:1, 1:3, 1:5 and 1:7 were prepared using fusion method. The prepared solid dispersions were characterized for their drug content, phase solubility studies, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), x-ray diffraction, and in-vitro dissolution studies. All the formulations showed marked improvement in the solubility and dissolution rate of drug which may be due to decrease in crystallinity of drug and additives. It was concluded that prepared solid dispersion of the Domperidone with PEG can improve the solubility and dissolution rate of the drug.

  Rosiglitazone is a poorly water-soluble (BCS class II) antidiabetic drug. Due to the poor water solubility of this drug, its bioavailability is dissolution rate-limited. The purpose of this study was is to increase the solubility of Rosiglitazone (RG) in aqueous media by solid dispersion (SD) technique with Poloxamer (PXM) 188 and Poloxamer (PXM) 407 by using the kneading method. The RG-PXM solid dispersion system was characterized by Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transform-infrared spectroscopy (FT-IR) and Scanning electron microscopy (SEM), and in vitro dissolution studies. No chemical interaction was found between RG and PXM 188 or PXM 407. The results from DSC, XRD and SEM studies show that PXM 188 or PXM 407 inhibits the crystallization of RG. The SDs prepared in this study were found to have better dissolution rates in comparison to intact RG and physical mixture of PXM 188 or PXM 407. It was found that the optimum weight ratio for drug: Carrier is 1:5 for PXM 188 and 1:6 for PXM 407. Key-Words: Solubility, Rosiglitazone, Solid dispersion

Flurbiprofen Non-steroidal anti-inflammatory drugs (NSAIDS) drug has half-life of about 3 to 6 hrs. The present study aims to formulate and evaluate poorly soluble drug Flurbiprofen using solid dispersion based tablet. Various studies have been done in attempt to improve the solubility’s of Poorly water soluble drugs. The advent of solid dispersion technique provides a unique approach to particle size reduction and increased rates of dissolution. The compatibility studies of the drug and polymers were studied by IR spectroscopy and results suggested no interaction between drug and polymers. Solid dispersions of Flurbiprofen were prepared by common solvent method using Hydroxy Propyl Cellulose (HPC), Polyvinyl Pyrrolidone K-30(PVP) and Mannitol Fast dissolution observed with Mannitol as compared to HPC and PVP. Formulations F3, F6 and F9 containing PVP, HPC and Mannitol along with drug in 1: 6 ratios were used to formulate tablets. Formulation F9 containing drug and Mannitol showed highest dissolution of 81.11% in 1 hour  due to amorphous nature of drug in presence of polymer. Formulation F3 containing drug and PVP in 1 : 6 ratio showed 73.05% drug release  because of the formation of aggregates. Formulation F6 containing drug and HPC showed only 61.65% drug release due to the crystalline of the drug, low solubility of the drug. Results indicate that formulations prepared by the technique of solid dispersion showed increase in the dissolution of Poorly water soluble drug. Key word: Solid dispersion; Flurbiprofen; Micronization; Compatibility studies.