过氧苯甲酰凝胶的研制和体外评价

Preparation and in vitro Evaluation of Benzoyl Peroxide Gel

制备了一种过氧苯甲酰凝胶,并与原研制剂进行体外等效性评价。采用琼脂凝胶扩散法测定凝胶中药物的扩散系数(K),并以此为指标用单因素试验筛选出自制凝胶的处方组成。所得优化处方中采用d(0.9)为5.86μm过氧苯甲酰原料药,含泊洛沙姆407 0.3%,卡波姆980 1.5%。根据过氧苯甲酰在不同介质中的饱和溶解度结果筛选接收介质。以市售凝胶剂班赛~?为对照,比较自制凝胶与原研制剂体外释放曲线的相似性,结果显示二者一致性良好(相似因子为72)。以猪皮为屏障进行体外透皮释放试验,HPLC法测定接收液、皮肤表面和皮肤层内过氧苯甲酰浓度,以及皮肤内的苯甲酸浓度。结果显示,自制凝胶与原研制剂中绝大部分药物都滞留在皮肤表面,皮肤中均检出少量过氧苯甲酸和苯甲酸。自制凝胶和市售凝胶的体外释放行为和体外透皮释放特性相似,提示自制凝胶在体外具有相同的有效性。

The aim of the present work was to develop a benzoyl peroxide（BPO）（5%） gel for skin acne vulgaris treatment, and the evaluation of in vitro equivalance to the reference listed drug（RLD）, Benzihex AC, was carried out. The formulations of the gel were formulated by employing Carbopol 980 as hydrophilic matrix and poloxamer 407 as sorbefacient. Optimization of formulation was supported by agar diffusion method and the following factors were investigated through single factor screening at three levels： the partical size of BPO（100-400 mesh number）, the concentration of Carbopol 980（1.0%-2.0%） and poloxamer 407（0.1%-0.3%）. The response variables was the diffusion distance in agar. The optimized gel had similar in vitro release profiles to the RLD based on the similarity factor（f2）. The delivery amounts of BPO into and through the pig skin from the optimized gel were compared to those from RLD. Both gels showed consistent behavior： the stratum corneum uptake and skin penetration of BPO from the two gels were generally comparable. Taken together, the results of this research provided a generic BPO gel that was in vitro equivalent to the RLD.