(M1030-04-23) Use of Mega Beads in Designing a Single Unit Biphasic Dosage Form

Purpose: There is an unmet need for dose personalization of drugs which are highly potent, chronically administered and have narrow therapeutic indices. Mega Beads are solid, single units, spherical beads and are 3.0-5.0 mm in size. The following experiments describe the development of a biphasic drug delivery system from a single bead.

Methods: Preparation of Core Beads: Drug-Avicel based Mega Bead cores were manufactured by extrusion/spheronization using MG-55 screw extruder and a Fuji spheronizer. Bead cores were designed for 5, 10 and 15 mg strength of a water-soluble drug. Beads were sifted through a set of screens where each drug strength was prepared from a specific bead size range. Drug Layering Process: Drug layering onto bead cores was conducted using an O’Hara Labcoat M50 equipped with a 19” coating pan. Drug strengths of the bead cores were adjusted to half the overall dose, followed by an enteric coat (composed of alcoholic mixture of Eudragit L100-55®). Drug layering continued onto the enteric coat to reach the intended dose strength, followed by a color coat. Drug Release Studies: USP dissolution apparatus II was used with initial 750 mL of 0.1N hydrochloric acid at 37.0°C to examine the outer layer immediate release portion of the bead for 2 hours. The dissolution medium pH was adjusted to 6.0 using 200 mL of 200mM phosphate buffer and sampling was continued for additional 2 hours. A marketed drug product made of capsule-filled beads of the same drug was evaluated for comparison.

Results: Dissolution of the three strengths of Mega Beads demonstrated biphasic release patterns where half the drug doses (48%-52%) were released in the acidic media within 30 minutes. Mega Bead cores did not release any enteric coated drug for the rest of the 2 hours test in acidic media. The enteric part of the Mega Beads was completely released when the pH of the dissolution was adjusted to pH value of 6.0, (Figure 2).

Conclusion: A targeted biphasic dissolution pattern was achieved from a single Mega Bead. Mega Beads provide an alternative delivery system to traditional, multi-unit beads filled in hard capsules, resulting in significant saving in manufacturing time and cost.

Figure 1. Design of biphasic mega bead formulation.