A novel method for in situ preparation of injectable biodegradable microspheres from the copolymer, poly(lactide-co-glycolide) (PLGA), without incorporating unacceptable organic solvents is described. The delivery system is a dispersion of PLGA microglobules ('premicrospheres' or 'embryonic microspheres') in an acceptable vehicle mixture (continuous phase) and whose integrity is maintained by the use of appropriate stabilizers. A solution of PLGA, triacetin, a model protein (cytochrome c), PEG 400, and Tween 80 (oil phase 1) is added dropwise with continuous homogenization to Miglyol 812-Span 80 solution (oil phase 2), thereby inducing phase separation (coacervation) of PLGA and forming PLGA microglobules (containing cytochrome c) dispersed in the continuous phase. This novel drug delivery system (NDDS) is a dispersion and has a viscous consistency, but is sufficiently syringeable. When injected, it comes in contact with water from an aqueous buffer or physiological fluid and, as a result, the microglobules harden to form solid matrix type microparticles entrapping cytochrome c (in situ formed microspheres). Cytochrome c is then released from these microspheres in a controlled fashion. The composition, rationale, and optimization of the NDDS are described here. Various formulation variables such as the PLGA concentration and type and the substitution of the continuous phase by a fresh oil phase 2 influenced the characteristics of this system. A preliminary investigation of the reproducibility and stability of the NDDS, as well as the physical stability of the encapsulated cytochrome c, revealed that these characteristics were not adversely affected.

Antifungal Agents↗

PubMedDate not supplied

Effectiveness of some tablet disintegrants in an insoluble direct compression base.

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Drug Combinations↗

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[Efforts toward the formulation of the therapeutic stereoisomer of ibuprofen].

In an on going effort to optimize ibuprofen antiinflammatory therapy, development studies on the active stereoisomer of ibuprofen have been conducted. The effects of pharmaceutical processing on the racemate (RAC-ibuprofen) and the enantiomer (S(+)-ibuprofen) were investigated. The formulation of the new stereospecific system, was impossible using wet granulation. The pharmaceutical development of S(+)-ibuprofen using direct compression appeared as a practical solution to this problem. The biopharmaceutical properties of the resulting tablets were well within pharmacopeia requirements. Nevertheless, mixing S(+)-ibuprofen with the excipients induced a drop in the enthalpy of fusion and after compaction, a low temperature eutectic appeared on the differential scanning calorimetry endotherms. Aging studies indicated that the raw material and pharmaceutical mixtures of S(+)-ibuprofen should be stored under strictly controlled conditions or processed immediately.

Ibuprofen↗