Melt Dispersion Adsorbed onto Porous Carriers: An Effective Method to Enhance the Dissolution and Flow Properties of Raloxifene Hydrochloride.

The objective of the present investigation is to enhance the dissolution and flow properties of raloxifene hydrochloride (RXH), a biopharmaceutical classification system class II drug. Melt dispersion of RXH with polyethylene glycol (PEG) 6000 was prepared by the fusion method. The melt dispersion was then adsorbed onto a porous adsorbent, Neusilin, by the melt adsorption method. Response surface methodology was employed to establish the design space for formulation variables such as the ratio of RXH to PEG 6000 in melt dispersion and amount of porous adsorbent to melt dispersion. Differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and accelerated stability techniques were utilized to characterize formulations. Negative Gibbs free energy values indicated spontaneous solubilization of RXH in PEG 6000. The time required for 80% of drug release from optimized formulation was <20 min compared with plain RXH. Accelerated stability studies confirmed the stabilization of amorphous melt dispersion in nanopores (nanoconfinement) of inorganic silicate Neusilin. Melt dispersion, adsorbed on porous carriers, is a promising technique to improve the dissolution characteristic as well as flow properties of drug molecules.

Spray dried solid dispersion of repaglinide using hypromellose acetate succinate: in vitro and in vivo characterization.

OBJECTIVE: This research study attempted to develop spray-dried solid dispersion, to enhance the solubility of repaglinide, an antidiabetic drug. SIGNIFICANCE: Aqueous solubility plays a major role in drug delivery because any chemical entity has to be in a dissolved state at the site of absorption, in order to get absorbed. Solid dispersion (SD) is one of the widely used techniques to enhance solubility and hence dissolution rate of poorly soluble drugs. METHODS: Repagnilide, in hypromellose acetate succinate (HPMCAS) solution, was dried by spray drying to obtain spray-dried solid dispersion (SDSD). Plackett-Burman and Box-Behnken designs were used for screening formulation as well as process parameters, and optimization respectively. DSC, XRD, SEM were carried out to confirm the preparation of solid dispersion. SDSD was evaluated for in vitro dissolution, flow properties, Percentage yield and in vivo oral glucose tolerance test. RESULT: Spray dried solid dispersion comprising (w/w) drug:polymer ratio of 1:3.82, 2.56% of aerosil and inlet temperature of 90 °C, corresponded to the best formulation obtained in this work. It showed t 85% of less than 15 min and a significant reduction in blood glucose level in rats as compared to pure drug and marketed formulation. CONCLUSION: Thus, it can be concluded that spray-dried solid dispersion prepared using HPMCAS is a useful technique for solubility and dissolution enhancement of repaglinide.

Solid dispersion adsorbate technique for improved dissolution and flow properties of lurasidone hydrochloride: characterization using 32 factorial design.

The aim of the present study was to improve the dissolution and flow properties of lurasidone hydrochloride (LH) by solid dispersion adsorbate (SDA) technique. Solid dispersions (SDs) of LH were prepared by fusion method using Poloxamer P188. The melt dispersion was adsorbed onto the porous carrier Florite (calcium silicate). A 32 factorial design was employed to quantify the effect of two independent variables, namely ratio of carrier (Poloxamer 188) and LH in SD and ratio of adsorbent (Florite) to SD. SDA granules of LH were studied for flow properties and characterized using differential scanning calorimetry, scanning electron microscopy, and X-ray diffraction. Tablets of optimized composition of SDA granules (equivalent to 20 mg of drug) and plain tablets were prepared by direct compression method. The dissolution studies were carried out in Mcllvaine buffer (pH 3.8) as per USFDA guidelines and characterized for parameters such as percent dissolution efficiency, t50, and Q30. Tablets prepared from SDA granules showed almost four-fold increase in cumulative percentage drug release as compared to tablets prepared from plain LH. The value of dissolution efficiency was enhanced from 49.60% for plain tablets to 94.15% for SDA tablets. SDA granules did not show any change in drug release and X-ray diffraction pattern after storage at 40 °C/75% of RH for 3 months, which confirms that Florite prevented conversion of drug from amorphous form to crystalline form improving physical stability of the amorphous state of LH.