To determine the effect of in vitro gastrointestinal digestion on the release and antioxidant capacity of encapsulated and nonencapsulated phenolics carob pulp extracts, unripe and ripe carob pulp extracts were microencapsulated with polycaprolactone via double emulsion/solvent evaporation technique. Microcapsules' characterization was performed using scanning electron microscopy and Fourier transform infrared spectrometry analysis. Total phenolics and flavonoids content and antioxidant activities (ORAC, DPPH, and FRAP) were evaluated after each digestion step. The release of phenolic acids and flavonoids was measured along the digestion process by HPLC-MS/MS analysis. The most important phenolics and flavonoids content as well as antioxidant activities were observed after gastric and intestinal phases for nonencapsulated and encapsulated extracts, respectively. The microencapsulation of carob polyphenols showed a protective effect against pH changes and enzymatic activities along digestion, thereby promoting a controlled release and targeted delivery of the encapsulated compound, which contributed to an increase in its bioaccessibility in the gut.

Background Metformin hydrochloride is a biguanide derivative that has been widely used to treat type 2 diabetes in humans. In veterinary medicine, metformin has shown increasing potential for diabetes treatment in different species, such as equids, dogs, cats and rabbits. It is highly hydrophilic, with incomplete gastrointestinal absorption and very large variability in absolute bioavailability between species, ranging from 4% in equids to 60% in humans. Metformin also shows a short half-life of approximately 2 h in dogs, cats, horses and humans. The objectives of this study were to evaluate a poly (lactic acid) (PLA) metformin microparticle formulation to test in rabbits and conduct a pharmacokinetics study of intravenous (SIV) and oral solution (SPO) metformin administration and oral PLA microparticle (SPLA) administration to rabbits to evaluate the improvement in the metformin pharmacokinetics profile. Results Metformin-loaded PLA microparticles were characterized by a spherical shape and high encapsulation efficiency. The results from Fourier transform infrared (FTIR) spectroscopy suggested the presence of interactions between metformin and PLA. X-Ray diffraction (XRD) analysis corroborated the results from the differential scanning calorimetry (DSC) studies, showing that metformin is present in an amorphous state within the microparticles. Physicochemical characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via hydrogen bonding interactions. The pharmacokinetic study in rabbits showed sustained-release characteristics from the prepared microparticles with a delay in the time needed to reach the maximum concentration (Tmax), decreased Cmax and bioavailability, and increased mean residence time (MRT) and half-life compared to the pure drug solution. Conclusions Metformin-loaded PLA microparticles showed optimal and beneficial properties in terms of their physicochemical characteristics, making them suitable for use in an in vivo pharmacokinetic study. The pharmacokinetic parameters of the metformin microparticles from the in vivo study showed a shorter Tmax, longer MRT and half-life, decreased Cmax and the prolonged/sustained release expected for metformin. However, the unexpected decrease in bioavailability of metformin from the microparticles with respect to the oral solution should be evaluated for microparticle and dose design in future works, especially before being tested in other animal species in veterinary medicine.

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Background: Metformin hydrochloride a biguanide derivative has been widely used in the treatment of type 2 diabetes in humans. In veterinary medicine, metformin has been increasing his potential in different species as equids for insulin dysregulation, dogs and cats with diabetes. It is a highly soluble hydrophilic drug, shows incomplete absorption from the gastrointestinal tract and the absolute bioavailability is 40-60 % with a short biological half-life of 1.5-1.6 h in humans. In this study, to improve its efficacy a sustained-release microparticles of metformin was developed by loading within poly lactic acid (PLA) polymer followed by an in vivo pharmacokinetics study in rabbits. Results: Pharmacokinetic study in rabbits showed the sustained-release characteristic from the prepared microparticles with delayed time to reach maximum concentrations Tmax, decreased Cmax, increased Mean Residence Time (MRT) and half-life compared to the pure drug solution. Physicochemical characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via hydrogen bonds and that the drug was transformed to an amorphous state. Conclusions: The The pharmacokinetics parameters resulted in delayed Tmax, increased MRT and t1/2, decreased Cmax of metformin from microparticles that show promise for prolonged/sustained release of metformin after oral administration in different animal species affected by insulin disorders. PLA microparticles provided sustained release of the drug, and these systems can be useful as drug carriers for hydrophilic drugs in long term disease treatment such as diabetes.