Pharmaceutial Studies On ACA

Acquired Immune Deficiency Syndrome(AIDS), which has caused significantthreat to people's health, draws great attention from all over the world. ACA is a newchemical entity extracted from Chinese traditional medicine. The results ofpharmacological action in its vitro study showed that ACA has great potentialities asan anti-AIDS drug. According to the physico-chemical property of slight solubilityand hydrolytic tendency in water, this pharmaceutical research on ACA providedoptions to different dosage forms based on the improvement of its solubility andstability. Furthermore, the study of prescription, technology, quality standards, andstability demonstrated the potentialities of ACA being a drug, which laid thefoundation of its drug reaction.During the research and development of a new drug, solubility is one of the mostimportant factor that researchers should pay attention to. It improves drugs' absorptionand effect that highly water soluble drugs often dissolute well in gastrointestinal fluid.Many drugs cannot reach therapeutic concentration even in saturation due to theirslight solubilities. ACA is almost insoluble in water. To increase the solubility iscrucial in its pharmaceutical studies. This research used pharmaceutical technology insolubilization of ACA. Compared with solid dispersion and inclusion complex, theresult manifested that it was more effective in solubilization using inclusion complex,the solubility of which increased to more than 200 times. Moreover, different kinds ofcyclodextrin and technology was studied to determine the optimized condition ofinclusion complex preparation.ACA is prone to hydrolyze on account of esters in its structure. The stability ofACA inclusion complex was studied. The result showed that water solution of ACAinclusion complex had low stability, which cannot meet the requirement ofpharmaceutical application by raising the concentration of ACA, adding organicreagent, adding stabilizing agents and adjusting pH value. The stability of solid ACAinclusion complex was prior to that of its water solution according to stress testing. Inconclusion, ACA inclusion complex should be prepared in solid dosage form.The study of ACA solubilization and stabilization gave evidence to option ofdosage forms, according to which variety of forms were designed, including sterile powders for injection, and tablets.There are sterile powders for injection by freeze drying and by subpackaging,which is of rapid drug reaction, reliable effect and high bioavailability. Freeze dryingpreparation of ACA inclusion complex was studied firstly; formula and technologywas determined. Considering that the process and residual water (1%-5%) may causeincrease of related substance, we examined the stability of the agents by stress testing.The result showed that related substance had increased to more than 5% in thecondition of high temperature (60℃) for 10 days, and had increased obviously in theaccelerating condition (40℃), which manifested low stability of sterile powders forinjection by freeze drying. According to the results above, sterile powders forinjection by subpackaging was studied, which had the same dosage and package.What is more, oral drug delivery of ACA inclusion complex was designed, whichis the simplest and easiest way of drug administration. Because of small bulk,accurate dosage and easy production, solid oral dosages forms have many advantagesover other types of oral dosage forms. ACA inclusion complex tablets werecompacted. After a series of selection, formulation was finally determined. We made acomparison between preparation though wet granulation and preparation of pressingtablets directly. The result showed that preparation of pressing tablets directly is ofmore beautiful appearance, greater stability, quicker dissolution and easier production.It can be concluded that ACA inclusion complex tablets absorbed moisture easily,which means a kind of moisture-proof package should be applied.The dosage of sterile powders for injection and tablets was determined to 10mgACA in every unit based on the result of solubilization. The formula can be adjustedaccording to clinical dosage of ACA after pharmacology experiment without anychange of dosage forms.We established the HPLC determination method of content and related substance,which is accurate, precise and of high reproducibility. The excipients and degradationproducts do not interfere the determination of ACA, therefore it is good to control thequality of ACA inclusion complex tablets and sterile powders for injection bysubpackaging. We prepared three batches of sample to undertake the quality control,and each index was consistent with the claim.We studied the stability of ACA inclusion complex tablets and sterile powdersfor injection by subpackaging as well , including stress testing, accelerated testing andlong-term testing. The definitive result disclosed that the appearance, content, related substance and other index were all corresponded with claim. The preparation is stable,which provided science proof for the manufacture, package, storage and transport.Otherwise, during pharmaceutical studies on ACA, we have provided sample forexperiment of toxicology, pharmacodynamics and so on many times.