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.
Fu
X C
XC
Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China. fuxc@zucc.edu.cn
Wang
G P
GP
Liang
W Q
WQ
Chow
M S S
MS
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