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

Drug Dev Ind Pharm. 2012 Sep;38(9):1068-76. doi: 10.3109/03639045.2011.638302. Epub 2011 Dec 10.


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.

Publication types

  • Comparative Study

MeSH terms

  • Bronchodilator Agents / chemistry
  • Chemical Phenomena
  • Delayed-Action Preparations / chemistry*
  • Drug Compounding
  • Excipients / chemistry*
  • Fatty Acids / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Mechanical Phenomena
  • Particle Size
  • Pressure
  • Solubility
  • Tablets
  • Tensile Strength
  • Theophylline / chemistry


  • Bronchodilator Agents
  • Delayed-Action Preparations
  • Excipients
  • Fatty Acids
  • Tablets
  • glyceryl behenate
  • Theophylline