Sustained-release solid dispersion of pelubiprofen using the blended mixture of aminoclay and pH independent polymers: preparation and in vitro/in vivo characterization

Abstract

The present study aimed to develop the sustained-release oral dosage form of pelubiprofen (PEL) by using the blended mixture of 3-aminopropyl functionalized-magnesium phyllosilicate (aminoclay) and pH-independent polymers. The sustained-release solid dispersion (SRSD) was prepared by the solvent evaporation method and the optimal composition of SRSD was determined as the weight ratio of drug: EudragitV R RL PO: EudragitV R RS PO of 1:1:2 in the presence of 1% of aminoclay (SRSD(F6)). The dissolution profiles of SRSD(F6) were examined at different pHs and in the simulated intestinal fluids. The drug release from SRSD(F6) was limited at pH 1.2 and gradually increased at pH 6.8, resulting in the best fit to Higuchi equation. The sustained drug release from SRSD(F6) was also maintained in simulated intestinal fluid at fasted-state (FaSSIF) and fed-state (FeSSIF). The structural characteristics of SRSD(F6) were examined by using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), indicating the change of drug crystallinity to an amorphous form. After oral administration in rats, SRSD(F6) exhibited the prolonged drug exposure in plasma. For both PEL and PEL-transOH (active metabolite), once a day dosing of SRSD(F6) achieved oral exposure (AUC) comparable to those from the multiple dosing (3 times a day) of untreated drug. In addition, the in vivo absorption of SRSD(F6) was well-correlated with the in vitro dissolution data, establishing a good level A in vitro/in vivo correlation. These results suggest that SRSD(F6) should be promising for the sustained-release of PEL, thereby reducing the dosing frequency.ARTICLE HISTORY

Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine

“…As shown in Table 2, CB is freely soluble in lower pH values while practically insoluble in water and higher pH which comes in agreement with previous studies. 27) A direct relationship is evident between pH and solubility of CB, with solubility decreasing as the pH increases which confirms the poor solubility of CB in intestinal pH (6.8) and accounts for its poor bioavailability. Addition of 1% SLS to phosphate buffer (pH 6.8) resulted in marked increase in CB solubility in this buffer, thereby would be added to the release medium in this study to achieve sink conditions.…”

“…The dispersion filled membrane was introduced into the dissolution apparatus cups using 1000 mL phosphate buffer pH 6.8 containing 1% SLS to maintain sink conditions due to poor solubility of CB in phosphate buffer. 27) The release study was carried out at 37±0.5°C, and the stirring shafts were rotated at a speed of 100 rpm. Three milliliter samples were withdrawn periodically at predetermined time intervals of 5, 10, 15, 30, 45 and 60 min and replaced instantly by equal amount of fresh release medium to maintain a constant volume.…”

“…The release study was done in a USP type II apparatus rotated at 100 rpm at a temperature of 37±0.5°C. The acid stage comprised the use of 750 mL 0.1 N HCl buffer as a release medium for 2 h, after which the pH was adjusted to pH 6.8 with 250 mL 0.2 M sodium triphosphate buffer 21,28,29) and the experiment was continued for 6 h. One percent SLS was added to achieve sink conditions in pH 6.8. Samples were withdrawn at 0.25, 0.5, 0.5,1, 1.5, 2, 2.5, 3, 4, 6 and 8 h, filtered and analyzed using the same method described earlier The release profiles were compared using similarity factor (f2) defined by the following equation 30)…”

“…Thus, increasing its release in intestinal pH in vitro will probably lead to enhanced drug levels in blood stream. 27,53) However, enhanced CB intestinal release is not adequate to prove the potential success of the prepared cubosomal dispersion in vivo. Thus assessing the effect on blood clotting and haemostasis of the prepared formula in vivo is of equal if not much importance for consideration when assessing cubosomal dispersions.…”

Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement

“…SNMSD could be categorized under controlled release formulation; the use of various mathematical models in describing drug release from solid dispersion including zero-order, first-order, Higuchi, Hixson–Crowell, and Korsmeyer–Peppas models was well recognized and reported. 44 – 47 Specifically, a solid dispersion using SOL could improve dissolution due to solid-state transformation as well as micellization. The use of zero-order, first-order, Higuchi, Hixson–Crowell, and Korsmeyer–Peppas models has been successfully described for drug release from SOL-based solid dispersion.…”