The Study Of Site-specific Bioadhesive Preparation Of Actinomycin D

ActinomycinD(AMD), a natural antitumor antibiotic, is best known for its effectiveness as an inhibitor of transcription. It has been employed in the treatment of several types of highly malignant human tumors in clinic, most notably in Wilm's tumor, chorioadenoma destruens, gestational choriocarcinoma and malignant kidney germinoma. It has been reported that chorioadenoma destruens be treated by AMD in combination with radiotherapy and surgery has achieved long-term remissions and cures in 90% of patients. It was also be certified that AMD has strongly toxicity by clinical and pharmacological experimentation, such as lower grade or midrange bone marrow depression and skin or mucous membrane exanthema maculosum. So the clinical usefulness of AMD is limited by the toxicity of AMD to host cells. It has been reported that AMD has therapeutic action for cancer of the cervix and ovarian cancer. Designing it into bioadhesive preparation can improve the local drug concentration, reduce the dose and keep the drug sustained release by locating the drug preparation into vagina or uterus of patients. So AMD bioadhesive preparation will not only decrease side effects of AMD systemic administration but also avoid the suffering of hysterectomia from early cancer patients.In the study of AMD bioadhesive tablets, the bioadhesive time was used to optimize the ratios of hydroxypropyl cellulose (HPC) and carbopol 934 (CP934); orthogonal design was used in the process of preparation and selection of different formulas, the evaluation criterion is bioadhesive force and T₅₀; the bioadhesive tablets were prepared by wet granulation and compression of mixed powers; the paddle method according to China Pharmacopoeia (2005) was used to evaluate the release rate of AMD bioadhesive tablets; the mucous membrane permeation absorption experiment was used to determine the permeability of AMD bioadhesive tablets in vitro. The results showed that the optimum formulation with desirable release process and bioadhesive force was obtained; the content uniformity was consistent with pharmacopoeia standard; the accelerating stability test showed that the optimum formulation was stable in the condition of air-tight, drying and avoiding light; the release of AMD from the bioadhesive tablets was agree with Higuchi equation; the drug release was corresponded to Fick's diffusion mechanism, the release rate decreased with the increase of the amount of carbopol 934 (CP934) included in formulation; the peak transit dose is 26.49±1.52 (%) over the 24h test period.In the study of AMD bioadhesive films, orthogonal design was used in the process of preparation and selection of different formulas, the evaluation criterion is appearance of films and mucous membrane permeation absorption in vitro. The content uniformity and dissolve time of the AMD bioadhesive films were conducted. The results showed that the prepared films were flexible, well-distributed in color and size; the peak transit dose of the optimum formulation is 38.21±0.02 (%) over the 24h test period, the content uniformity and dissolve time were consistent with pharmacopoeia standard.In conclusion, the study of actinomycin D site-specific bioadhesive tablets and films in this paper provide foundations for further study of AMD preparation with higher efficiency and lower toxicity in future.