Midazolam-sirupus, formulation and pharmacodynamic efficacy

Due to its pharmacokinetic and pharmacodynamic properties (sedation, amnesia and relief of anxiety) Midazolam has become a comm only used agent for conscious sedation of children before diagnostic or therapeutic procedure or before induction of anesthesia. Con sidering the advantage of oral administration to avoid the additional trauma of starting an IV in the child, and the fact that there is no ad equate dosage form (Midazolam - Syrupus) on the drug market in our country, the aim of the presented work was to formulate syrupus using syrupus b ase/aqueous solution of viscosity enhancer - HPMC, in combination with suitable sweetener, flavor, and preservatives, and to evaluate its q uality and stability. The pharmacodynamic efficacy/sedative effect of Midazolam HCl - Syrupus formulation was evaluated in 33 pediatric patients comp aring this with the efficacy of intramuscularly administered Midazolam HCl (35 pediatric patients) in accordance with the Ramsay scale for analgosedation. The formulation manifested good quality in respect to physical properties, physico-chemical parameters (pH value, relative dens ity, drug content, ingredients content) antimicrobial efficacy and microbiological quality according to Ph Eur 3. In the conditions chara cteristic of the second (II) climate zone, the dosage form was stable for four months. The sedative effect of orally administered Midazolam was manifested in a period necessary for surgical premedication (30 - 45 min). The majority of patients (71%) entered the second phase on the Ramsa y scale, when Midazolam was administered in a dose of 0.40 mg/kg

Bioinspired bioartifical polymer hybrid composites for propolis vaginal delivery II: formulation and characterization

In our previous work Box-Behnken experimental design was applied for formulation optimization of the thermoreversible mucoadhesive in situ vaginal hydrogels with propolis and optimized batches were identified. Optimized batches of bioartificial polymer hybrid composites (chitosan, Lutrol® F-127 and Lutrol® F-68 mixture)) (CP1, CP2, CP3) were prepared using so-called cold method. Formulation P3 (chitosan free) was prepared in order to evaluate the effect of chitosan on the physico-chemical and biopharmaceutical properties of the polymer hybrid composites (gels). The pH values of the gels were 4-4.5. The gelation temperature for all formulations was in a range of 29-33 o C. Total flavonoids content was above 95%. Increase in concentration of Lutrol® F-127 and Lutrol® F-68/Lutrol® F-127 ratio lead to a higher viscosity values and slower gel erosion/dissolution. The presence of chitosan increased gel viscosity and hence slow-down erossion/dissoluiton. Propolis release rate was the highest in P3 which released propolis within 5 h, corresponding to time of complete erosion. The same correlation between erosion process and drug release rate was observed in CP1-CP3, where prolonged propolis release for more than 10 h was achieved. Microbiological quality was in accordance with the requirements of Ph. Eur. 7. All formulations demonstrated adequate stability at 5 ± 3 °C during 6 months. Based on overall results it can be anticipated that bioartificial blended bioinspired polymer hybrid composites for propolis vaginal delivery could represent intelligent delivery systems with physicochemical and biopharmaceutical properties in favor or efficacious and safe therapy of vaginal infections

Elucidation of spheroid formation with and without the extrusion step

Spheroid formation mechanisms were investigated using extrusion-spheronization (ES) and rotary processing (RP). Using ES (cross-hatch), ES (teardrop), and RP (teardrop), spheroids with similar mass median diameter (MMD) and span were produced using equivalent formulation and spheronization conditions. During spheronization, the teardrop-studded rotating frictional surface, with increased peripheral tip speed and duration, produced spheroids of equivalent MMD and span to those produced by the cross-hatch rotating frictional plate surface. The roundness of these spheroids was also similar. RP required less water to produce spheroids of MMD similar to that of spheroids produced by ES. However, these RP spheroids were less spherical. Image analysis of 625 spheroids per batch indicated that the size distribution of RP spheroids had significantly greater SD, positive skewness, and kurtosis. Morphological examination of time-sampled spheroids produced by ES indicated that spheroid formation occurred predominatly by attrition and layering, while RP spheroids were formed by nucleation, agglomeration, layering, and coalescence. RP produced spheroids with higher crushing strength than that of ES-produced spheroids. The amount of moisture lost during spheronization for spheroids produced by ES had minimal influence on their eventual size. Differences in process and formulation parameters, in addition to size distribution and observed morphological changes, enabled a greater understanding of spheroid formation and methods to optimize spheroid production