Pharmacokinetic Appraisal of Carprofen Delivery from Intra-Articular Nanoparticles: A Population Modeling Approach in Rabbits

Osteoarthritis is frequently treated in veterinary settings with non-steroidal anti-inflammatory drugs (NSAID) such as carprofen (CP). Its action over the articular cartilage can be enhanced by increasing drug uptake into the cartilage, alongside its site of action, and anticipating its rapid distribution towards the bloodstream. A pharmacokinetic study to evaluate carprofen nanoparticles (NP) after intraarticular administration (IA) in rabbits was performed through a modeling allometric approach. The pharmacokinetic analysis of plasma profiles showed a rapid CP distribution outwards the synovial chamber but mainly remaining in plasma (Vc = 0.14 L/5 Kg), according to its high protein-binding. The absorption data modeling showed the occurrence of two different release–absorption rate processes after nanoparticle administration in the synovial space, i.e., a fast rate process causing a burst effect and involving the 59.5% of the total CP absorbed amount and a slow rate process, involving 40.5%. Interestingly, the CP burst effect inside the joint space enhances its diffusion towards cartilage resulting in CP accumulation in about three times higher concentrations than in plasma. In line with these results, the normalized-by-dose area under the concentration vs. time curve (AUC) values after IA were 80% lower than those observed after the intravenous. Moreover, the slower slope of the concentration–time terminal phase after IA administration vs. intravenous (IV) suggested a flip-flop phenomenon (0.35 h-1 vs. 0.19 h-1). Notably, CP clearances are predictive of the pharmacokinetic (PK) profile of CP in healthy humans (0.14 L/h/5 kg vs. 2.92 L/h/70 kg) although an over-estimation has been detected for cats or dogs (10 times and 4 times, respectively). This fact could probably be attributed to inter-species metabolic differences. In summary, despite the limited number of animals used, this study shows that the rabbit model could be suitable for a predictive evaluation of the release enhancement of CP-NP towards the biophase in arthritic diseases not due to sterical retention of the formulation

Release of Ropinirole from Acrylate-Vinylacetate Transdermal Formulations: Modulation Based on Polymer-Drug Interactions

Optimization of transdermal formulations requires solving simultaneous challenges as the selection of release polymers. The interactions between the formulation components must be taken as a way to modulate its performance. Selection of acrylic polymers with different functionalizations for the transdermal formulation of a tertiary amine drug (ropinirole HCl) have been investigated. Aim of this work is to characterize the influence over drug release of certain experimental interactions. Solubility-crystalization and pharmacopoeial release tests have been used to evaluate the influence of drug loading and the pH of the release media. Area under the curve of dissolved amounts and percentage of release have been used as discriminant variables in mutual influence with the physical state of the drug. Elucidation of release mechanisms has been performed with data fitting of relevant modelystic equations. Fickian release and erosion contribution have been related with drug loading and the risk of burst effects. In conclusion, a rationale to select the best suitable polymer for ropinirole HCl has been demonstrated in terms of efficiency and extent of release

Collaborative permeation of drug and excipients in transdermal formulations. In vitro scrutiny for ethanol: limonene combinations

Enhancement of skin permeation of drugs is affected by the simultaneous co-permeation of excipients that hinder the predictivity of in vitro tests. The collaborative effects of two permeation enhancers (ethanol and d-limonene) of a lipophilic drug (alprazolam) have been simultaneously assessed in human skin under different in vitro conditions: integrated setups of diffusion cell experiments with selective concentration gradients of permeants (asymmetric) or without (symmetric) have been combined with coadministration dosages (all-in-one) at different concentrations or short-time skin pretreatment to scrutiny this mutual performance. Findings: Drug permeation is increased under moderated supersaturation but reaches a stationary level above 33 % of its solubility. Ethanol in absence of a concentration gradient increases ca.5 times basal drug permeation. Limonene until 20 % permeates human skin proportionally to its donor concentration but its effect does not depend on ethanol in symmetric conditions and is based on skin imbibition rather than on a carry-on effect. Simultaneous permeation of ethanol and limonene reaches a stationary state after 1.5 h, enough time to achieve maximal enhancement of alprazolam permeation. Additive enhancement is based on ethanol solubilisation maximized by skin saturation of terpene. Complementary analyses of skin disruption published in the literature are in line with these assessments and consolidate them

Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study

Carprofen (CP), a non-steroidal anti-inflammatory drug (NSAID), is profusely used in veterinary medicine for its analgesic and anti-inflammatory activity. Some undesirable effects are associated with its systemic administration. Alternative local routes are especially useful to facilitate its administration in animals. The main aim of this paper is to validate the suitability of ex vivo permeation experiments of CP with porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) intended to be representative of naïve in vivo conditions. Chromatographic analysis of CP in membrane-permeated samples and drug-retained have been validated following standard bioanalytical guidelines. Then, recovery levels of drugs in tissue samples were assessed with aqueous phosphate buffered saline (PBS) buffer to preserve the histological integrity. Finally, as a proof of concept, a series of CP permeation tests in vertical Franz diffusion cells has been performed to evaluate permeation flux and permeability constants in all tissues, followed by a histological study for critical evaluation. Furthermore, synthetic tissue retention-like samples were prepared to verify the value of this experimental study. Results show linear relationships with good determination coefficient (R2 > 0.998 and R2 > 0.999) in the range of 0.78 to 6.25 mg/mL and 3.125 mg/mL to 100 mg/mL, respectively. Low limits of quantification around 0.40 µg/mL were allowed to follow permeation levels until a minimum of 0.40% of the locally-applied dose. This method showed a good accuracy and precision with values lower than 2%. After the recovery technique, reproducible values below 30% were achieved in all tissues, suggesting it is a non-damaging method with low efficiency that requires the use of further solvents to enhance the extraction percentages. After permeation and histology tests, no relevant peak interferences were detected, and no cell or tissue damage was found in any tissue. In conclusion, results demonstrate the suitability of this test to quantify the distribution of CP with good histological tolerability

Ex Vivo Permeation of Carprofen Vehiculated by PLGA Nanoparticles through Porcine Mucous Membranes and Ophthalmic Tissues

(1) Background: Carprofen (CP), 2-(6-chlorocarbazole) propionic acid, is used as an anti-inflammatory, analgesic and anti-pyretic agent and it belongs to the family of non-steroidal anti-inflammatory drugs (NSAIDs). CP has some adverse reactions in systemic administration; for this reason, topical administration with CP nanoparticles (CP-NPs) can be an optimal alternative. The main objective of this work is the investigation of ex vivo permeation of CP through different types of porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) to compare the influence of CP-NPs formulation over a CP solution (CP-Solution). (2) Methods: The ex vivo permeation profiles were evaluated using Franz diffusion cells. Furthermore, in vivo studies were performed to verify that the formulations did not affect the cell structure and to establish the amount retained (Qr) in the tissues. (3) Results: Permeation of CP-NPs is more effective in terms of drug retention in almost all tissues (with the exception of sclera and sublingual). In vivo studies show that neither of the two formulations affects tissue structure, so both formulations are safe. (4) Conclusions: It was concluded that CP-NPs may be a useful tool for the topical treatment of local inflammation in veterinary and human medicine

Biopharmaceutical Development of a Bifonazole Multiple Emulsion for Enhanced Epidermal Delivery

Efficient topical delivery of imidazolic antifungals faces the challenge of overcoming its limited water solubility and its required long-lasting duration of treatments. In this paper, a hydrophilic multiple emulsion (ME) of Bifonazole (BFZ) is shown to maximize its skin retention, minimize its skin permeation, and maintain an acceptable level of being harmless in vivo. The formulations were pharmaceutically characterized and application properties were assessed based on viscosity measurements. Non-Newtonian pseudoplastic shear thinning with apparent thixotropy was observed, facilitating the formulation retention over the skin. The in vitro release profile with vertical diffusion cells showed a predominant square-root release kinetic suggesting an infinite dose depletion from the formulation. Ex vivo human skin permeation and penetration was additionally evaluated. Respective skin permeation was lower than values obtained with a commercial O/W formulation. The combination of amphoteric and non-ionic surfactants increased the bifonazole epidermal accumulation by a factor of twenty. This fact makes the possibility of increasing its current 24 h administration frequency more likely. Eventual alterations of skin integrity caused by the formulations were examined with epidermal histological analysis and in vivo preclinical measurements of skin elasticity and water retrograde permeation. Histological analysis demonstrated that the multiple emulsions were harmless. Additionally, modifications of in vivo skin integrity descriptors were considered as negligible.There are no specific funding sources or universitary fellowship for this experimental work. Article processing charges were partially supported by University of Barcelona

Biopharmaceutical Development of a Bifonazole Multiple Emulsion for Enhanced Epidermal Delivery

Efficient topical delivery of imidazolic antifungals faces the challenge of overcoming its limited water solubility and its required long-lasting duration of treatments. In this paper, a hydrophilic multiple emulsion (ME) of Bifonazole (BFZ) is shown to maximize its skin retention, minimize its skin permeation, and maintain an acceptable level of being harmless in vivo. The formulations were pharmaceutically characterized and application properties were assessed based on viscosity measurements. Non-Newtonian pseudoplastic shear thinning with apparent thixotropy was observed, facilitating the formulation retention over the skin. The in vitro release profile with vertical diffusion cells showed a predominant square-root release kinetic suggesting an infinite dose depletion from the formulation. Ex vivo human skin permeation and penetration was additionally evaluated. Respective skin permeation was lower than values obtained with a commercial O/W formulation. The combination of amphoteric and non-ionic surfactants increased the bifonazole epidermal accumulation by a factor of twenty. This fact makes the possibility of increasing its current 24 h administration frequency more likely. Eventual alterations of skin integrity caused by the formulations were examined with epidermal histological analysis and in vivo preclinical measurements of skin elasticity and water retrograde permeation. Histological analysis demonstrated that the multiple emulsions were harmless. Additionally, modifications of in vivo skin integrity descriptors were considered as negligible

Comisión de terapias biológicas. ¿Qué nos aporta?

Objetivo: Evaluar el impacto general a nivel asistencial de una comisión de terapias biológicas, en enfermedades inflamatorias inmunomediadas, mediante los hábitos de prescripción, los estudios prebiológicos y la inmunización. Método: Se realizó un estudio cuasiexperimental sobre todos los pacientes naïve mayores de edad que iniciaron tratamiento con un medicamento biológico por enfermedad inflamatoria inmunomediada el año anterior y el año posterior a la creación de la comisión de terapias biológicas. Resultados: Se incluyeron un total de 31 pacientes estudiados en 2016 y 40 pacientes estudiados en 2018. La prescripción de medicamentos inhibidores del factor de necrosis tumoral α se redujo en 2018 (80,6% versus 45,0%;

Análisis de la evaluación única y continuada en Biofarmacia y Farmacocinética-I

Podeu consultar la Setena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/43352La construcción del Espacio Europeo de Educación Superior (EEES) tiene como objetivo disponer de un espacio abierto en el que no existan obstáculos a la movilidad de estudiantes, titulados, profesores y personal de administración. El sistema se articula en torno al reconocimiento de titulaciones y otras calificaciones de educación superior, la transparencia (un sistema de titulaciones comprensibles y comparables organizado en tres ciclos) y la cooperación europea en la garantía de la calidad Ante este gran reto, la enseñanza universitaria ha tenido que reorganizarse y los planes de estudio de cada facultad han tenido que adaptarse a las nuevas exigencias del EEES. Además las metodologías docentes centran su interés en un seguimiento más tutorizado del alumno, para garantizar su aprendizaje, no sólo en la adquisición de conocimientos sino también de competencias

Evaluación del aprendizaje en Biofarmacia y Farmacocinética en evaluación única y continuada

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Transcurridos unos años de la implantación del Plan Bolonia en las universidades españolas, y concretamente en la facultad de Farmacia de la Universidad de Barcelona, cabe preguntarse si estos cambios de planes de estudio, cambios metodológicos docentes y la tutorización del alumnado han revertido en la adquisición de un mayor conocimiento en las materias que se imparten. Con este objetivo, en la unidad de Biofarmacia y Farmacocinética, en la cual se imparten dos asignaturas obligatorias de 3 y 6 créditos ECTS (Biofarmacia y Farmacocinética I y II, respectivamente), y con un nº de alumnos muy elevado (316-360) se ha realizado un estudio de evaluación del aprendizaje en conocimientos de los alumnos que han seguido evaluación única y/o continuada..