Prediction of drug release from HPMC matrices: effect of physicochemical properties of drug and polymer concentration.
A working equation to predict drug release from hydroxypropyl methylcellulose (HPMC) matrices was derived using a training set of HPMC matrices having different HPMC concentration (w/w, 16.5-55%) and different drugs (solubilities of 1.126-125.5 g/100 ml in water and molecular volumes of 0.1569-0.4996 nm(3)). The equation was log(M(t)/M( infinity ))=-0.6747+1.027 log t -0.1759 (log C(s)) log t +0.4027 (log V) log t -1.041C(H) +0.3213 (log C(s)) C(H) -0.4101 (log V) C(H) -0.3521 (log V) log C(s) (n=263, r=0.9831), where M(t) is the amount of drug released at time t, M( infinity ) the amount of drug released over a very long time, which corresponds in principle to the initial loading, t the release time (h), C(s) the drug solubility in water (g/100 ml), V the volume of drug molecule (nm(3)), and C(H) is HPMC concentration (w/w). The benefit of the novel model is to predict M(t)/M( infinity ) values of a drug from formulation and its physicochemical properties, so applicable to the HPMC matrices of different polymer levels and different drugs including soluble drugs and slightly soluble drugs.
Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China. fuxc@zucc.edu.cn
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D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D010078:Oxazines; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D011108:Polymers; D012044:Regression Analysis; D012995:Solubility; D013607:Tablets
D003692:Delayed-Action Preparations; D005079:Excipients; D010078:Oxazines; D004364:Pharmaceutical Preparations; D011108:Polymers; D013607:Tablets; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose