Characterization and in vivo evaluation of ocular bioadhesive minitablets compressed at different forces

• Published in: Journal of controlled release Vol. 89; no. 2; pp. 329 - 340
• Main Authors: Weyenberg, W., Vermeire, A., Remon, J.P., Ludwig, A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29.04.2003; Elsevier
• Subjects: Adhesives - chemistry; Adhesives - pharmacokinetics; Adult; Analysis of Variance; Biological and medical sciences; Compressive Strength; Cornea - drug effects; Cornea - metabolism; Dissolution; Drug Evaluation, Preclinical - methods; Drum dried waxy maize starch and polyacrylic acid; Female; General pharmacology; Humans; In vivo study; Male; Medical sciences; Middle Aged; Ocular minitablet; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Swelling behavior; Tablets; Ocular minitablet; In vivo study; Drum dried waxy maize starch and polyacrylic acid; Swelling behavior; Dissolution; Human; Compression; Pharmaceutical technology; Swelling; Normal; Corn starch; In vitro; In vivo; Friability; Acrylic acid polymer; Dosage form; Active ingredient; Tablet; Porosity; Ocular minitablet: Drum dried waxy maize,starch and polyacrylic acid: Dissolution; Bioadhesive system; Release; Intraocular administration; In vivo 'study: Swelling behavior
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(03)00130-5

The influence of the compression force on the physical properties, the in vitro release and the in vivo behavior of ocular minitablets is evaluated in the present study. The bioerodible minitablets (Ø 2 mm, 6 mg) were produced at different compression forces. The crushing strength, friability, water uptake, hydration and swelling of the minitablets both in vitro as well as in vivo after application in the cul-de-sac were evaluated. The friability remained below 1% only for the minitablets made at 0.500 and 0.750 kN. The crushing strength measured was 3.53±0.98, 12.34±1.69 and 18.64±2.37 N for minitablets made at 0.250, 0.500 and 0.750 kN, respectively. The full hydration time equalled 20 and 30 min for minitablets compressed at 0.250 kN and 0.500–0.750 kN, respectively. Increasing the compression force resulted in a decreased swelling capacity. The in vivo release was evaluated in healthy volunteers using a non-invasive method to measure the apparent sodium fluorescein concentration in the tearfilm–cornea compartment as a function of time. The longest residence time of the fluorescent tracer at the administration site was obtained by the minitablets compressed at 0.750 kN. The in vitro release was evaluated with three different dissolution methods: the reciprocating cylinder method, vials in an oscillatory shaking bath and a static method with vials. The best correlation with the in vivo behavior of the matrix minitablets was obtained with the shaking bath method.