Development and evaluation of sustained-release Compritol^® 888 ATO matrix mini-tablets

Abstract

Context: Sustained-release mini-tablets are a potentially suitable for paediatric drug delivery or as multi-particulate dosage forms.

Objective: To evaluate the potential for developing lipophilic matrix mini-tablets and to assess the effects of Compritol^® 888 ATO concentration on drug release from differently sized mini-tablets prepared by direct compression.

Methods: A formulation comprising theophylline as a model soluble drug, 15% w/w Compritol^® 888 ATO as the inert matrix-forming agent, with dibasic dicalcium phosphate anhydrous and lactose as diluents was evaluated by producing 12 mm tablets at a range of compression speeds and forces. The same formulation and further formulations with 25, 35 or 45% w/w Compritol^® 888 ATO were evaluated by producing 2, 3 and 4 mm mini-tablets.

Results and Discussion: Drug release from matrix tablets was sustained over a period of 12 hours and release rate varied according to the compression force and speed employed. The rate of drug release from matrix mini-tablets was more rapid and increasing Compritol^® 888 ATO concentration resulted in slower release rates. The rate of drug release from matrix mini-tablets was inversely proportional to mini-tablet size (2 mm > 3 mm > 4 mm). Drug release from the matrix tablets and mini-tablets followed square-root of time kinetics.

Conclusion: Tailored drug release from matrix mini-tablets may achieved by altering the size of mini-tablet or level of Compritol^® 888 ATO in the formulation and this may have potential in the development of paediatric formulations or multi-particulate dosage forms.

Keywords::

• Glyceryl behenate
• lipophilic matrix
• paediatric drug delivery
• multi-particulate dosage form
• rotary press simulator
• theophylline