| Acne is a chronic inflammatory skin disease involving the hair follicle sebaceous glands,mostly involving young men and women of 15 to 30 years old.Above 90% men and women in adolescence can have different levels of skin lesions,which seriously affect their appearances.At present,the routine medicines used in the treatment of acne include anti-keratinization,antibiotics,antiandrogen and corticosteroid hormone drugs.In recent years,the photodynamic therapy(PDT)combining photosensitizer(such as aminolevulinic acid hydrochloride)is widely used in the treatment of acne,with a large number of clinical studies on the curative effect and safety evaluation finding it accurate and of long duration,especially for moderate to severe acne.However,in current marketplace,there is only 5-Aminolevulinic acid hydrochloride powder could be as the photosensitizer to cooperate the photodynamic therapy,and the mixture solution has some disadvantages like poor transdermal effect,massive drug loss and inconvenience of administration.Therefore,this article proposes a in-situ gel for external use in order to solve the above problems.In this article,the method of HPLC for the determination of 5-Aminolevulinic acid hydrochloride in-situ gel was established.And the method of HPLC for the determination of 5-Aminolevulinic acid hydrochloride in-vitro percutaneous penetration assay was also established.The methodologies were investigated separately,including precision,stability,and recovery,etc.,and the results met the relevant requirements of Chinese Pharmacopoeia.Using appearance and gelation temperature as the indicators,the prescription 5-Aminolevulinic acid hydrochloride in-situ gel agent was screened,and the preliminary prescription was confirmed as the following: 5 g 5-Aminolevulinic acid hydrochloride,20 g poloxamer 407,4 g poloxamer 188,10 g glycerol,0.1 g ethylparaben.The method for in-vitro percutaneous penetration assay was established,and the penetration enhancer of 5-Aminolevulinic acid hydrochloride in-situ gel was selected according to the assay results.The in-vitro percutaneous penetration assay used vertical Franz diffusion cell,and isolated SD mice belly skin as in-vitro transdermal barrier and saline isotonic solution as receptor fluid.Different kinds of penetration enhancers were evaluated and compared,using the accumulate osmolality and the permeability enhancement ratio(ER)as the indicators.The final prescription is as follows: 5 g 5-Aminolevulinic acid hydrochloride,20 g poloxamer 407,4 g poloxamer 188,10 g glycerol,0.1g ethylparaben,3 g azone,1 g propylene glycol.The performance,pH,and percutaneous permeability of the in-situ gel were also investigated,resulting with the uniform fine appearance,good spreadability,pH between 5.5 and 6.5,as well as around 50 mg g-1 of 5-Aminolevulinic acid hydrochloride in-situ gel.The results of impact factor tests(including the high temperature test,high humidity test and strong light exposure test)showed that high temperature and high humidity had no effect on sealed 5-Aminolevulinic acid hydrochloride in-situ gel,but the light had a great influence,which indicated that the gel should avoid light for storage.In 3 months of accelerated assay and long-term assay,all the indicators of 5-Aminolevulinic acid hydrochloride in-situ gel found no significant change,and its quality is stable.Further accelerated tests and long-term tests are still ongoing.Preclinical safety experiments were conducted by using rabbit skin irritation test,showing that 5-Aminolevulinic acid hydrochloride in-situ gel had no skin irritation or allergic reaction on rabbit.In this thesis,the 5-Aminolevulinic acid hydrochloride in-situ gel with reasonable,feasible and stable prescription and preparation process was developed,and the quality of the obtained in-situ gel was stable with no skin irritation.It was required to avoid light for storage.It provided a new clinical drug formulation for the treatment of Acne. |
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