[Dosage forms of phytogenic drugs]. / Zubereitungsformen pflanzlicher Arzneimittel.

Herbal drug formulation is a challenge in pharmaceutical technology due to the complex physicochemical properties of these multicomponent materials. Potential instabilities of the pharmacologically active and coactive substances as well as incompatibilities and interactions of the extracted compounds and excipients have to be considered. Microbial contamination of the applied plant material might limit the shelf life of the products. Using state of the art methods in formulation stable preparations are obtained; additionally compliance of drugs might be enhanced due to simplified application or better sensorial quality. Nowadays, besides traditional pharmacopoeial aqueous, ethanolic, or (partially) dried extracts fluid, semisolid, or solid dosage forms of these extracts are in use, for example syrups, juices, drops, liniments, gels, ointments, creams, suppositories, tablets, coated tablets (dragees) as well as soft and hard gelatine capsules.

Toxicity of a particulate formulation for the intraperitoneal application of mitoxantrone.

Mitoxantrone (MXN) has demonstrated therapeutic efficacy in the intraperitoneal treatment of malignancies. However, severe local toxicity is dose limiting. Therefore, a particulate formulation of MXN, the drug incorporated in albumin microspheres, was evaluated concerning tolerability. Survival rates as well as alterations in body weight, food intake, water intake, urine volume, urine specific gravity, urine protein content, and complete blood count were observed following single or multiple intraperitoneal injections of MXN solution, dispersions containing MXN-loaded microspheres or unloaded microspheres, and the injection vehicle to female and male Sprague-Dawley rats. Applied MXN dosage was equivalent to 30 mg/m2 body surface area. Unloaded microspheres were well tolerated without signs of toxicity. Application of MXN solution or MXN-loaded microspheres resulted in similar survival rates (56% 9 weeks after single injection) and in a comparable bone marrow toxicity (mainly leucopenia). Body weight, food and water intake as well as urine volume were decreased following application of MXN solution, whereas a progressive gain in weight and no remarkable alterations in nutrition and urine excretion were noted after administration of MXN-loaded and unloaded microspheres, or of the injection vehicle. In conclusion, intraperitoneal injection of MXN incorporated in albumin microspheres exhibits in part less toxicity than conventional treatment.

Evaluation of mitoxantrone-loaded albumin microspheres following intraperitoneal administration to rats.

Mitoxantrone has demonstrated therapeutic efficacy in the regional treatment of intraperitoneal malignancies. However, severe local toxicity was dose limiting. Consequently, a new injectable sustained delivery formulation of mitoxantrone has been developed: the drug was incorporated (8.2 w/w%) in highly hydrophilic albumin microspheres. In vitro drug release profile was modified by matrix crosslinking extent. The extractable amount of residual crosslinking agent (glutaraldehyde) in the microspheres was lower than 6 ppm. Mitoxantrone concentration in peritoneal fluid and plasma was determined up to 72 h after intraperitoneal administration of 30, 60 and 120 mg mitoxantrone per m2 body surface area as solution and in the form of a dispersion containing mitoxantrone-loaded microspheres to rats. Data analysis revealed sustained release of mitoxantrone from microspheres into peritoneal fluid in all dosage groups. The initial high drug levels in peritoneal fluid and plasma observed after application of mitoxantrone in the solution form were prevented by administration of the drug incorporated in microspheres. However, tumoricidal drug levels in peritoneal fluid were maintained over a comparable time span. In addition, preliminary toxicity data suggest a superior local tolerability of mitoxantrone-loaded microspheres. The dose of intraperitoneally administered mitoxantrone might be increased from 30 to 60 mg per m2 body surface area using the slow release formulation. In conclusion, the described microsphere drug delivery system for mitoxantrone might overcome dose-limiting drug toxicity.