Dissolution Rate Of Felodipine Research Articles

Microencapsulation of Solid Dispersions of Felodipine and Characterization of Release Mechanism

The study was aimed at increase the solubility of poorly soluble drug Felodipine and formulating it in sustained release dosage form. Solid dispersion of drug was prepared using Poly vinyl pyrollidone (PVP) and hydroxyl propyl methyl cellulose (HPMC) as inert hydrophilic carriers by kneading method. A 17-fold increase in dissolution rate of Felodipine was observed with solid dispersion prepared with HPMC. Optimized solid dispersion was further characterized by Powder X-ray diffraction (PXRD) which suggest transformation of crystalline Felodipine in amorphous form and Fourier transform infrared spectroscopy (FTIR) suggesting no possible interaction. Sustained release microcapsules of Felodipine were formulated using ethyl cellulose (EC) and Eudragit® RL 100 (EDRL) as coating material with solid dispersion of Felodipine as core by emulsion solvent evaporation method. Gelatin was used as microencapsulating agent employing coacervation-phase separation technique. Microcapsules from all the batches were found to discrete, spherical and free flowing and % entrapment efficiency was found to be in range of 88% to 96%. All the batches of microcapsules showed sustained release curve in pH 7.4 phosphate buffer up to eight hours with microcapsules prepared with gelatin giving Felodipine release up to 86% after 8 hrs. XRD pattern studies of the microcapsules made of gelatin showed drug still present in the amorphous form and thus maintaining its solubility in the microcapsule system.

Development of a novel starch with a three-dimensional ordered macroporous structure for improving the dissolution rate of felodipine.

In this study, silica nanospheres with different particle sizes were used as hard template for synthesis of a starch with a novel three-dimensional ordered macroporous structure (3DOMTS). As a pharmaceutical adjuvant, 3DOMTS was used to improve the dissolution rate and oral relative bioavailability of water-insoluble drugs. Felodipine (FDP) was chosen as a model drug and was loaded into the 3DOMTS by solvent evaporation. FDP loading into 3DOMTS with different pore sizes was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimeter (DSC), powder X-ray diffractometer (PXRD) and Fourier-Transform Infrared (FTIR). The results obtained showed that FDP was present in the pores in an amorphic or microcrystalline state. The in vitro dissolution results showed that 3DOMTS could effectively improve the dissolution rate of FDP in comparison with commercial common tablets. Pharmacokinetic results indicated that the oral relative bioavailability of self-made FDP-3DOMTS tablets were 184%, showing that 3DOMTS produced a significantly increased oral absorption of FDP. In conclusion, 3DOMTS exhibits the dual potential of improving the dissolution rate of poorly water soluble drugs and the novel filler produced by direct compression technology confirming that 3DOMTS will be useful for many applications in the field of pharmaceutics.

Felodipine nanosuspension: a faster in vitro dissolution rate and higher oral absorption efficiency

In the present work, nanocrystals were prepared to improve oral bioavailability of felodipine. Several important formulation factors and process parameters were explored, optimized and analyzed systematically. The prepared nanocrystals were characterized for morphology, particle size, zeta potential, possible crystallization changes, release behavior and oral absorption. The morphology of the obtained nanocrystals was found to be rod shape. The particle size and zeta potential were 140 ± 10 nm and -29.11 mV, respectively. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis indicated that felodipine had undergone crystal form transition. The dissolution rate of felodipine was significantly increased and the AUC0-t value of felodipine colloidal dispersion in beagle dogs was approximately 1.6-fold greater than that of the commercial tablets. Nanocrystals impose a faster dissolution rate and higher oral absorption efficiency than raw crystals, and show great potential as an effective strategy for improving oral bioavailability of poorly soluble drugs.

친수성고분자 및 비이온성 계면활성제를 이용한 펠로디핀 서방정제의 설계

Felodipine, a calcium-antagonist of dihydropyridine type, is a poorly water soluble drug and has very low bioavailability. As preceding studies, use of solid dispersion systems and surfactants(solubilizers) has been suggested to increase dissolution and to improve bioavailability of felodipine. But in case of solid dispersion systems, large amount of toxic organic solvents should be used and manufacturing process time become longer than conventional process. In case of using surfactants, as time elapsed, decreasing of dissolution rate of felodipine due to crystallization has been reported. In this study, Copovidon as a hydrophilic polymer and as a surfactant were combined to formulations if order to increase dissolution of felodipine and conventional wet granulation process were applied to manufacturing of formulations. The effect of Copovidon and on the dissolution oi felodipine was investigated in-vitro. When Copovidon and used simultaneously, the dissolution rate of felodipine was prominently increased compared with when used separately and the maximum increase in the dissolution of felodipine was 5.8 fold compared to control. This is most probably due to synergy effect by combination of Copovidon and . Felodipine sustained release tablets were successfully formulated using several grades of HPMC as a release retarding agent. The stability of felodipine sustained release tablet was evaluated after storage at accelerated condition() for 6months in HDPE(High density polyethylene) bottle. Neither significant degradation nor change of dissolution rate for felodipine was observed after 6months. In conclusion, felodipine sustained release tablet was successfully formulated and dissolution of felodipine, poorly water soluble drug, was prominently increased and also stability was guaranteed by using combination system of hydrophilic polymer and surfactant.

Preparation of a solid dispersion of felodipine using a solvent wetting method

A straightforward solvent wetting method was used to prepare felodipine solid dispersions in the presence of various carriers. Dichloromethane is not needed when HPMC solid dispersions were produced using the solvent wetting method. The amount of ethanol used to prepare solid dispersions did not have a significant effect on the dissolution rate of felodipine. The results of X-ray diffraction and thermal analysis indicated that the drug was in the amorphous state when PVP, HPMC, and poloxamer were used as carriers. The dissolution rates of felodipine in PVP, HPMC, or poloxamer solid dispersions were much faster than those for the corresponding physical mixtures. However, dissolution profiles were found to depend on the carrier used; the dissolution rate of felodipine increased slowly for solid dispersions prepared using HPMC, whereas rapid initial dissolution rates were observed for solid dispersions prepared using PVP or poloxamer. Increases in dissolution rates were partly dependent on the ratios of felodipine to carrier. No significant changes in crystal form were observed by X-ray diffraction or thermal analysis, and no significant changes in dissolution rate were observed when sorbitol and mannitol were used as carriers.

고체분산체에 의한 펠로디핀의 용출율 개선과 서방성 경구제제

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug

The surface-specific dissolution rates ( G-values) of two size fractions of felodipine, a sparingly soluble drug, at different concentrations of polysorbate 80 were compared, using a Coulter Counter Model TAII. The solubilities of the drug at these surfactant concentrations were determined photometrically. The dependence of particle-size on dissolution rate was also evaluated for a number of size fractions of felodipine at a low concentration of polysorbate 80, using the Coulter method. It was shown that the effect of particle fineness was stronger than could be predicted from the differences in initial surface area. The G-values for a number of felodipine qualities were calculated from dissolution data obtained by the USP XXI rotating paddle method at both low and high concentrations of the micellar solutions used. The data delivered by the two dissolution methods were in fairly good agreement. The higher polysorbate concentration gave the same discrimination of the size fractions tested, although higher G-values were obtained.