Dispersion and release of embelin from electrospun biodegradable, polymeric, membranes

In this work, microfiber meshes containing embelin, a poorly water-soluble bioactive agent, were prepared by solubilizing embelin in a biodegradable and biocompatible polymer matrix of poly(ε-caprolactone) (PCL). Plain or drug-loaded, highly porous, fibrous membranes with a high area-to-volume ratio were obtained by electrospinning. Non-woven microfibrous meshes were formed by uniform bead-free fibers with a mean diameter of 1.2 μm. Non-porous films were obtained by solution casting, and were used for comparison. The drug-loading content of the prepared systems was appropriate for topical applications. The thermal properties revealed that the crystallinity of embelin significantly decreased, the drug having almost completely dissolved in the PCL fibers. The in situ bioavailability of embelin, an antimycotic agent, is an important aspect to consider in topical drug applications. The drug-loaded systems presented different contact areas with the biological environment. When comparing the ability to expose embelin with the biological environment of the prepared systems, drug-loaded fibrous scaffolds showed a higher bioavailability of the bioactive agent because of an increase by 86% in the area-to-volume ratio, providing an effective area per unit mass that was 5.8-fold higher than that of the film. For the meshes, 90% embelin release was observed after 12h of exposure to phosphate-buffered saline, whereas for the films a comparable level of release occurred only after 72h.Fil: Cortez Tornello, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Tapia, Alejandro. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Veiga, Itiara G.. Universidade Estadual de Campinas; BrasilFil: Moraes, Ângela M.. Universidade Estadual de Campinas; BrasilFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cuadrado, Teresita Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

Preparation and Evaluation of Poly(Ethylene Glycol)–Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

A series of monomethoxy poly(ethylene glycol)–poly(lactide) (mPEG–PLA) diblock copolymers were designed according to polymer–drug compatibility and synthesized, and mPEG–PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug

The solution and solid state stability and excipient compatibility of parthenolide in feverfew

The objectives of this research were to evaluate the stability of parthenolide in feverfew solution state and powdered feverfew (solid state), and explore the compatibility between commonly used excipients and parthenolide in feverfew. Feverfew extract solution was diluted with different pH buffers to study the solution stability of parthenolide in feverfew. Powdered feverfew extract was stored under 40°C/0%∼75% relative humidities (RH) or 31% RH/5∼50°C to study the influence of temperature and relative humidity on the stability of parthenolide in feverfew solid state. Binary mixtures of feverfew powered extract and different excipients were stored at 50°C/ 75% RH for excipient compatibility evaluation. The degradation of parthenolide in feverfew solution appears to fit a typical first-order reaction. Parthenolide is comparatively stable when the environmental pH is in the range of 5 to 7, becoming unstable when pH is less than 3 or more than 7. Parthenolide degradation in feverfew in the solid state does not fit any obvious reaction model. Moisture content and temperature both play important roles affecting the degradation rate. A fter 6 months of storage, parthenolide in feverfew remains constant at 5°C/31% RH. However, ∼40% parthenolide in feverfew can be degraded if stored at 50°C/31% RH. When the moisture changed from 0% to 75% RH, the degradation of parthenolide in feverfew increased from 18% to 32% after 6-month storage under 40°C. Parthenolide in feverfew exhibits good compatibility with commonly used excipients under stressed conditions in a 3-week screening study

Stabilization of hot-melt extrusion formulations containing solid solutions using polymer blends

This study was aimed at enhancing the physical stability of the drug clotrimazole (CT) and the polymer contained within hot-melt extrusion (HME) films using polymer blends of hydroxypropyl cellulose (HPC) and poly(ethylene oxide) (PEO). The HME films were investigated for solid-state characteristics, moisture sorption, bioadhesivity, mechanical properties, glass transition temperature, release characteristics, and physical and chemical stability of the drug and the polymer within the HME films. The solid-state characterization of the drug and the polymer was performed using differential scanning calorimetry, x-ray diffractometry, and dynamic mechanical analysis. A texture analyzer was used to study the bioadhesive and mechanical properties of the HME films. The physical and chemical stability of the films, stored at 25°C/60% relative humidity or in a desiccator, was studied for up to 12 months. CT was found to be in solid solution within all of the formulations extruded. The physical stability of the drug and PEO in the HME films increased with increasing HPC concentration, but the bioadhesivity and flexibility of the PEO films decreased with increasing HPC concentration. Films containing HPC: PEO∶CT in the ratio of 55∶35∶10 demonstrated optimum physical-mechanical, bioadhesive, and release properties. In conclusion, polymer blends of HPC and PEO were used successfully to tailor the drug release, mechanical and bio-adhesive properties, and stability of the HME films

Influence of Formulation and Processing Factors on Stability of Levothyroxine Sodium Pentahydrate

Stability of formulations over shelf-life is critical for having a quality product. Choice of excipients, manufacturing process, storage conditions, and packaging can either mitigate or enhance the degradation of the active pharmaceutical ingredient (API), affecting potency and/or stability. The purpose was to investigate the influence of processing and formulation factors on stability of levothyroxine (API). The API was stored at long-term (25°C/60%RH), accelerated (40°C/75%RH), and low-humidity (25°C/0%RH and 40°C/0%RH) conditions for 28 days. Effect of moisture loss was evaluated by drying it (room temperature, N2) and placed at 25°C/0%RH and 40°C/0%RH. The API was incubated with various excipients (based on package insert of marketed tablets) in either 1:1, 1:10, or 1:100 ratios with 5% moisture at 60°C. Commonly used ratios for excipients were used. The equilibrium sorption data was collected on the API and excipients. The API was stable in solid state for the study duration under all conditions for both forms (potency between 90% and 110%). Excipients effect on stability varied and crospovidone, povidone, and sodium laurel sulfate (SLS) caused significant API degradation where deiodination and deamination occurred. Moisture sorption values were different across excipients. Crospovidone and povidone were hygroscopic whereas SLS showed deliquescence at high RH. The transient formulation procedures where temperature might go up or humidity might go down would not have major impact on the API stability. Excipients influence stability and if possible, those three should either be avoided or used in minimum quantity which could provide more stable tablet formulations with minimum potency loss throughout its shelf-life

Moisture Uptake of Polyoxyethylene Glycol Glycerides Used as Matrices for Drug Delivery: Kinetic Modelling and Practical Implications

Gelucire 50/13, a polyoxyethylene glycol glyceride mixture, has been widely used in drug delivery, but its moisture uptake behaviour is still poorly understood. In this study, the effects of relative humidity, temperature, and drug incorporation on the moisture uptake of Gelucire are reported in relation to their practical implications for preparation of solid dispersions using this materialPeer reviewe