Purpose: Mini-tablets are becoming a more attractive dosage form in oral drug delivery, specifically for the pediatric and geriatric populations, due to their flexibility in dosing and uniform size and shape. Both pediatric and geriatric patient populations can benefit from this unique dosage form by alleviating the administration of a liquid dosage form that must be administered multiple times a day and/or is unpleasant tasting. The small nature of mini-tablets makes powder flow a critical attribute that can affect properties of the final tablets. Benecel™ PH DC has already been proven to be the superior controlled release polymer to aid in powder flow when producing matrix mini-tablets. This study examines the ability to manipulate the release profile of mini-tablets in addition to tastemasking when using an aqueous ethylcellulose dispersion in conjunction with a high molecular weight hypromellose.
Methods: Dry blends containing theophylline, Benecel™ K100M PH DC, microcrystalline cellulose, and magnesium stearate, were compressed to a target tablet weight of 7 mg using multi-tip tooling (consisting of ten 2 mm tips per tablet punch) on a 16 station Manesty Betapress at a speed of 54 rpm, and a constant compression force of 10 kN. The mini-tablets were then coated with Aquarius™ Control ECD. Samples were taken during the coating run at 5%, 10%, 15%, and 20% weight gains. Tablets from each weight gain, as well as un-coated tablets, were tested for dissolution in pH 6.8 phosphate buffer. Additionally, the tastemasking effectiveness of Aquarius™ Control ECD coated mini-tablets was determined using an Astree electronic tongue.
Results: The photographs of coated mini-tablets demonstrate a defect free coating system when as much as a 20% weight gain was applied (Table 1). The drug release profile of theophylline mini-tablets was successfully modified with the application of Aquarius™ Control ECD at 5%, 10%, 15%, and 20% weight gains (Figure 1). As the weight gain of the coating increases, the more modified the release profile becomes. By varying the weight gain of the coating, complete drug release can be extended beyond that of the uncoated mini-tablet up to nine hours at the highest weight gain. Aquarius™ Control ECD also provided tastemasking of the unpleasant tasting API.
Conclusion: The major benefit of coating matrix mini-tablets with Aquarius™ Control ECD is the ability to modify drug release. The Aquarius™ Control ECD film coating system demonstrated its versatility through its ability to modulate the release profile of the mini-tablets over a wide time range while simultaneously providing taste-masking. The combination of Benecel™ K100M PH DC polymer and an ethylcellulose dispersion coating such as Aquarius™ Control ECD is a practicable formulation approach to achieving patient friendly dosage forms based on mini-tablets.
Quyen Schwing– Senior Team Leader, Ashland Specialty Ingredients, Wilmington, Delaware
Kapish Karan– Team Leader, Ashland Specialty Ingredients, Wilmington
Thomas Dürig– Senior Director, Ashland Specialty Ingredients, Wilmington, Delaware