Expedited Development of Diphenhydramine Orally Disintegrating Tablet through Integrated Crystal and Particle Engineering

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Abstract

A palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), was developed using an integrated crystal and particle engineering approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including fast in vivo disintegration, and acceptable bitterness and grittiness. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed using 15 g of DPH and in two months. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.

Original languageEnglish (US)
Pages (from-to)3399-3408
Number of pages10
JournalMolecular pharmaceutics
Volume14
Issue number10
DOIs
StatePublished - Oct 2 2017

Bibliographical note

Funding Information:
We are grateful for resources from the University of Minnesota through the Minnesota Supercomputing Institute. Some of the experiments were performed at the University of Minnesota I.T. Characterization Facility, which receives partial support from the NSF through the NNIN program. We thank Kunling Wang for her help in collecting Raman spectroscopic data and members of the taste panel for their contributions. C.W. thanks Ms. Lily Liu for her useful comments during the preparation of this manuscript.

Publisher Copyright:
© 2017 American Chemical Society.

Keywords

  • direct compression
  • formulation development
  • orally disintegrating tablet
  • sweet salt

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