Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

Solidification of Nanostructured Lipid Carriers Loaded Testosterone Undecanoate: In Vivo and In Vitro Study

To enhance the bioavailability of testosterone undecanoate (TU) and overcome the current problem of soft capsules (Andriol Testocaps®), Nano-structured lipid carriers (NLC) for TU was developed. First, suspension of TU-loaded NLC (TU-NLC) was prepared by high pressure homogenization; then adsorbent or a protective agent β-cyclodextrin was used to solidify the suspension through a vacuum system; finally, the solid powder of TU-loaded NLC (solid TU-NLC) was filled into hard capsules. The characteristics of solid TU-NLC, were investigated in vitro and vivo. The particle size of TU-NLC was about 273.3 nm, the potential was 0.156±0.04. Transmission electron microscope (TEM) revealed that the NLC was spherical and uniform. Differential scanning calorimetry (DSC) suggested the drug had been encapsulated into NLC lipid matrix. The drug release proved that solid TU-NLC showed a higher dissolution in vitro. The CaCO-2 cell permeability showed that solid TU-NLC could enhance trans-membrane absorption of the TU. Moreover, the AUC of solid TU-NLC formulations (4304±550.50 μg/L*min) was higher than commercial product Andriol Testocaps® (3075±372.50 μg/L*min). In conclusion, solid TU-NLC could enhance the rate of dissolution, and had a relatively higher bioavailability than Andriol Testocaps® in vivo Graphical Abstract.

Influence of hot alcohol extraction of Celery fruits on renal stones dissolution in vitro.

This study was carried out to investigate the effect of hot alcohol extraction activity of Apium graveolens fruits on the common Renal stones dissolution (Ca-OX ,Uric acid) kinds and volatile oils concentrations on Apium graveolens via HPLC were estimated. Fourteen compounds which were (α-pinene, Cineole, P- cymene, Terpinene, α- phellandrene, β-pinene, Geraneole, α-terpinole, Linalool, Menthone, Limonene, Myrcene, Camphen, Rutin) were measured. In regard to concentration, α -pinene has the highest concentration since it reaches 19.2 µg/ml, while the lower concentration was achieved with Camphen which was 6.3 µg/ml. Results of Ca-Ox renal stones treated with extract of Apium graveolens showed significant decrease in stone weight since highest weight decrease percentage, using the hot alcoholic extract reaches 17.02 % at 5 % concentration and in comparison with Rowantinex drug, the results showed a high similitude between the hot alcoholic extract at 5% concentration and Rowantinex drug in respect of percentage of renal stones dissolution, so hot alcohol extraction of apium gravedens in 5% concentration was the best and active in dissolution Ca-OX at first degree and uric acid at second degree.