Amorphous solid dispersions in high-swelling, low-substituted hydroxypropyl cellulose for enhancing the delivery of poorly soluble drugs.

Amorphous solid dispersions (ASDs) based on water-insoluble hydrophilic polymers can sustain supersaturation in their kinetic solubility profiles (KSPs) compared to soluble carriers. However, in the limit of very high swelling capacity, the achievable extent of drug supersaturation has not been fully examined. This study explores the limiting supersaturation behavior of ASDs of poorly soluble indomethacin (IND) and posaconazole (PCZ) based on a high-swelling excipient, low-substituted hydroxypropyl cellulose (L-HPC). Using IND as a reference, we showed that the rapid initial supersaturation buildup in the KSP of IND ASD can be simulated through sequential IND infusion steps, however at large times the KSP of IND release from ASD appears more sustained than direct IND infusion. This has been attributed to potential trapping of seed crystals generated in the L-HPC gel matrix thus limiting their growth and rate of desupersaturation. Similar result is also expected in PCZ ASD. Furthermore, the current drug loading process for ASD preparation resulted in the agglomeration of L-HPC based ASD particles, producing granules of up to 300-500 µm (cf. 20 µm individual particle), with distinct kinetic solubility profiles. This feature makes L-HPC particularly suitable as ASD carriers for fine tuning of supersaturation to achieve enhanced bioavailability for poorly soluble drugs.

Efficacy and safety of nanoparticles of glibenclamide and organomodified layered double hydroxides in diabetics rats.

Glibenclamide (GB) is an important drug in the treatment of type II diabetes mellitus (DM II); however, its low solubility causes variability in its oral bioavailability, negatively affecting the pharmacological treatment. Nanoparticles (NP) of GB and organophilized Layered Double Hydroxide (LDH) were developed to improve oral bioavailability and tested in streptozotocin-induced diabetic rats to evaluate therapeutic efficacy and safety. Blood glucose was measured for 12 h or after 28 days of treatment. In addition, body weight, water and feed consumption, hematological, biochemistry and morphological parameters and markers of oxidative stress were determined. After the treatment, GB with LDH normalized the blood glucose level, indicating a better release profile. Water and feed intake and body weight of animals treated with GB and GB with LDH were closer to the normoglycemic group and did not indicate signs of toxicity of the nanoparticles. The biochemical, hematological and histological results also showed no significant changes related to nanotoxicity. The combination of GB with LDH proved to be critical in the oxidative balance, as it reduced the oxidative stress of vascular tissue. In conclusion, NPs are a potential controlled release system for the treatment of DM II.