Evaluation of hydrophilic matrix tablets based on Carbopol(®) 971P and low-viscosity sodium alginate for pH-independent controlled drug release.
BACKGROUND
The aim of this study was to evaluate matrix tablets containing different ratios of Carbopol(®) 971P (CP) to low-viscosity sodium alginate (SA) and assess their suitability for pH-independent controlled drug release.


METHODS
Two processing methods (physical mixing, PM and spray-drying, SD) were applied before compaction and the release from corresponding matrices was compared. The release from CP-SA PM matrices was also investigated using three model drugs (paracetamol, salicylic acid, and verapamil HCl) and two dissolution media (0.1 N HCl or phosphate buffer, pH = 6.8), and the release rate, mechanism, and pH-dependence were characterized by fitting of Higuchi and Peppas models, and evaluation of similarity factor. Furthermore, swelling behavior of CP-SA matrix tablets was studied for evaluating its impact on drug release.


RESULTS
The processing method (SD or PM) markedly affected the drug release from CP-SA matrices. ANOVA tests showed significant effects of the CP:SA ratio and drug type on the release rate (expressed by the constant, K(H), from Higuchi model) and of the dissolution medium on the release mechanism (expressed by the exponent, n, from Peppas model). Similarity factor (f₂) indicated that the CP:SA ratios ≥ 25:75 and ≥ 50:50 were suitable for pH-independent release of paracetamol and salicylic acid, respectively, although for verapamil HCl, the matrix with low CP:SA ratio (0:100) showed remarkably reduced pH-dependence of release. Swelling parameters (water uptake and mass loss) were significantly changed with experimental variables (CP:SA ratio, medium, and time) and were in good correlation with drug release.


CONCLUSIONS
Matrix tablets based on CP and SA form a potentially useful versatile system for pH-independent controlled drug release.
Department of Pharmaceutical Sciences and Pharmaceutics, Applied Science University, Amman, Jordan. nizoubi@yahoo.com
Nizar M
NM
Al-Zoubi
Hatim S
HS
AlKhatib
Wasfy M
WM
Obeidat
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000179:Acrylates / Q000008:administration & dosage*; D000464:Alginates / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D020723:Glucuronic Acid / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000008:administration & dosage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D020156:Salicylic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics; D014783:Viscosity
D000179:Acrylates; D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D013607:Tablets; C492577:carbopol 971P; D000082:Acetaminophen; D020723:Glucuronic Acid; D014700:Verapamil; D020156:Salicylic Acid