Captopril gastrointestinal therapeutic system coated with cellulose acetate pseudolatex: evaluation of main effects of several formulation variables.
Maintenance of constant drug levels in the body for those drugs that are used in management of hypertension is extremely beneficial. This can be successfully achieved by delivering the antihypertensives as osmotically-controlled drug-delivery system that essentially eliminates the influence of pH on the drug release. The main objective of this study was to evaluate the main effects of the formulation variables on the release of captopril from osmotically-controlled drug-delivery system coated with a custom-made cellulose acetate (CA) pseudolatex reported earlier. A secondary objective was to identify a suitable antioxidant for incorporating in the formulation as the drug undergoes metal-catalyzed oxidative degradation. The drug showed good stability (> or = 90% intact captopril) in solution in the presence of ascorbic acid for a period of 48 h. A seven-factor, 12-run Plackett-Burman screening design was employed to study the main effects of amounts of Polyox(R) N10 and N80, Carbopol(R) 934P and 974P, sodium chloride, orifice size, and % coating weight gain. The response variable was cumulative percent of drug released in 12 h, Y(3), with constraints on lag time Y(1) and time for 50% drug released Y(2)amount of sodium chloride (1.97).
Khan
M A
MA
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA. khan@cortex.ama.ttuhsc.edu
Sastry
S V
SV
Vaithiyalingam
S R
SR
Agarwal
V
V
Nazzal
S
S
Reddy
I K
IK
D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry; D002138:Calibration; D002216:Captopril / Q000008:administration & dosage* / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D008962:Models, Theoretical; D009995:Osmosis; D012995:Solubility
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D004337:Drug Carriers; C005062:acetylcellulose; D002482:Cellulose; D002216:Captopril