Study On The Preparation And Quality Control Of The Glucosamine Conventional And Hollow Suppositories

Osteoarthritis (osteoarthritis, OA) is a chronic joint disease which caused byarticular cartilage degenerative diseases and secondary bone hyperplasia, and itmainly related to the degeneration of articular cartilage by abnormal synthesis ofproteoglycan. Osteoarthritis especially occured in middle-aged and old people,and it has becomed a global common diseases at present. Glucosamine is naturalamino monosaccharides which presents in the human body and especially inarticular cartilage, it is an important component of proteoglycan of articularcartilage, it can specifically act on the articular cartilage, which play the role ofconservation and restoration. Glucosamine on sale are all the oral preparationswhich limit the efficacy by first-pass elimination of hepatic. In this study, we willprepare new dosage forms for glucosamine hydrochloride which are simplepreparation, stable quality, safe and effective, low cost for the treatment ofosteoarthritis, and they are conventional type suppository and hollow typesuppository.By investigating the various influence factors of the prescription andpreparation process for glucosamine conventional type suppository and hollow type suppository, we preferred the best prescription and process. At the sametime, reference2010edition of Chinese pharmacopoeia, we carried out fullquality control of glucosamine conventional type suppository and hollow typesuppository by using different inspection methods and analysis techniques fortheir stability, effectiveness and safety.In formulation design, we selected fat-soluble semi-synthetic fatty acidglycerides as a matrix, because its nature is opposite to glucosamine, and it canquickly dissolve and release the drug to play the systemic efficacy. Using singlefactor screening method preferred amount of Tween-80with dissolution as theevaluation index. In this study, we choosed the simple hot melt method forpreparation and optimized the process parameters，investigating temperature fordrug join, mixing time and speed, filling temperature and speed, coolingtemperature and time by the single factor screening method. On the above basis,hollow suppository is preferably the best formulation and preparation program byorthogonal test.According to the2010Chinese Pharmacopoeia two appendix about therelevant provisions of suppository, we have established the study on qualitystandard of the two types of glucosamine suppositories including appearance,physical and chemical identification, weight variation, pH, melting point,disintegration test, assay, dissolution, stability and so on. Due to the lack ofultraviolet absorption peak for glucosamine, we have to establish the pre-columnderivatization HPLC method for the determination of the two suppository drugcontent. In this study, we first used OPA pre-column derivatization HPLC method,then comparing to2-naphthoyl chloride pre-column derivatization HPLC method,and they are both accurately and efficiently. The latter had high sensitivity, lowdetection limit, and it may contribute to the further monitor for plasmaconcentration of glucosamine. The determination of suppository dissolution referenced to the2010edition of Chinese Pharmacopoeia about dissolution testof second method (paddle method).1. The best formulation and preparation for the two types of glucosaminesuppositories: the two types of suppositories were prepared withsemi-synthetic fatty acid glycerides as the substrate, glycerol as the lubricant,and Tween-80as the absorption-promoting agent in an amount of4%. Theconventional type suppository was prepared by adding drugs at thetemperature of60℃, stirring for15minutes with a speed of30r/min, fillingtemperature at35℃with the medium-speed, the cooling temperature at4℃for20min.When preparating the hollow suppository, first we filled with purematrix, second a rod with diameter of0.15cm and coating with glycerolplastic vertically inserted into the matrix with a depth of1.5cm after5minutes cooling at room temperature, then pulled out the plastic rod aftercooling and get a the hollow shell, the next quantitative injected13.5mgglucosamine for propylene glyco as the dispersion medium containing,finally sealed the tail, cooled, and got it.2. Study on quality control of the two types of glucosamine suppositories:Appearance, physical and chemical identification, weight variation, pH,melting point, disintegration test of the two types of glucosaminesuppositories are in line with the relevant provisions of the Pharmacopoeia;glucosamine is in the range of1-50μg/ml with a good linear relationship(r=0.9998) by OPA pre-column derivatization HPLC method, and it is in therange of0.1-1000μg/ml (r=0.9993) by2-naphthoyl chloride pre-columnderivatization HPLC method. The determination results for content of the twomethods both conformed to the rules. The dissolution test results showed thattwo types of suppositories in vitro dissolved rapidly,1h of conventional typesuppository cumulative release percentage in vitro is100.04%and20min of hollow type suppository cumulative release percentage in vitro is98.51%. Itis obvious that hollow type suppository dissolved more rapidly thanconventional type suppository. The stability test results showed that the twosuppositories are stable within6months at room temperature or within10days under highlight or high temperatures.In this study, the preferred formulation design and production process arereasonably and practicable, and the quality of the finished products are stable andcontrollable.