Bouriche, SihemAlonso-García, AngelaCárceles-Rodríguez, Carlos M.Rezgui, FaroukFernández-Varón, Emilio2022-10-212022-10-212021-09-25Bouriche S, Alonso-García A, Cárceles-Rodríguez CM, Rezgui F, Fernández-Varón E. An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits. BMC Vet Res. 2021 Sep 25;17(1):315http://hdl.handle.net/10668/4270Background 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/MetforminControlled-releaseMicroparticlesPharmacokineticsPolymeric-based formulationsDiabetes Mellitus, Type 2Calorimetry, differential scanningHalf-LifeSpectroscopy, Fourier transformifraredLactic acidMetforminaPreparaciones de acción retardadaMicroplásticosFarmacocinéticaDiabetes mellitus tipo 2Rastreo diferencial de calorimetríaSemividaEspectroscopía infrarroja por transformada de FourierÁcido lácticoMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Administration, IntravenousMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Administration, OralMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Pharmaceutical Preparations::Dosage Forms::Delayed-Action PreparationsMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Time::Half-LifeMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::MetforminMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Particle SizeMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::PolyestersMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Lagomorpha::RabbitsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Carnivora::Canidae::DogsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Perissodactyla::Equidae::HorsesMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Calorimetry::Calorimetry, Differential ScanningMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Pharmacokinetics::Biological AvailabilityMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Fourier AnalysisMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Physicochemical Processes::Hydrogen BondingMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Spectrophotometry::Spectrophotometry, Infrared::Spectroscopy, Fourier Transform InfraredMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Crystallography::X-Ray DiffractionMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::MetforminMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactates::Lactic Acidresearch article34563196Acceso abierto10.1186/s12917-021-03016-31746-6148PMC8467142