A patient-centric approach: Formulation of prolonged release microparticles to be used in oral suspensions for older patients with dysphagia

Valentyn Mohylyuk, Kavil Patel, Darragh Murnane, Craig Richardson, Fang Liu*

*Corresponding author for this work

Research output: Contribution to conferencePosterpeer-review

Abstract

Purpose Most oral dosage forms such as tablets and capsules are not suitable for older people with swallowing difficulties. Capsule opening and tablet crushing are commonly used to overcome this problem. In addition to safety and legal concerns, this approach cannot be applied to sustained release products because of the loss of their functionality, consequently causing dose dumping and, undesirable side effects and even toxicity. The number of appropriate medicines for older patients with swallowing difficulties is therefore limited because of the absence of suitable oral dosage forms. One of the most appropriate forms of medicines for patients with swallowing difficulties are liquid formulations. To overcome the described issues in older patients with dysphagia, the present study was aimed at the development of stable film-coated sustained release microparticles for use in redispersible multi-dose oral suspensions to facilitate swallowing. Methods Metoprolol succinate (Sinobio Chem. Co. Ltd., China) drug loaded and sustained release film-coated microparticles were prepared in a fluid-bed coater (Mini-Glatt, Glatt AG, Germany) using MCC-cores (Cellets 90, IPC Process-Centre GmbH, Germany) with 86.5 µm D50 particle size (laser diffraction method, Sympatec), HPMC (Methocel E5, Colorcon, UK), aqueous Eudragit NM 30 D (Evonik AG, Germany) based coating with admixture of talc (Pharma M, Imerys Talc, Italy) and magnesium stearate (Acros Organics, Belgium or Sudeep Pharma Pvt. Ltd., India). Oral liquid suspension vehicles were prepared by dissolving/mixing excipients in/with deionised water. Metoprolol succinate (MS) solubility in water and suspension vehicles was measured using shake-flask method (3 days at RT). Suspensions were prepared by adding the sustained release microparticles to different ready-to-use vehicles to obtain appropriate dose. Drug leakage from the coated microparticles in the suspension vehicle (Bottle-test) was carried out during shelf storage (1 month at RT). Dissolution tests of the microparticles before and after storage were performed using USP II method (50 rpm) in 500 ml of PBS pH 6.8 (Copley Scientific, UK). UV-absorption was measured (T80, PG Instruments Ltd., UK) at 274 nm. Results Sustained-release MS microparticles were produced by film coating using a fluid bed coater. The average particle size of the coated particles was < 200 µm. The achieved yield of coated non-agglomerated particles was more than 99%. The solubility of metoprolol succinate (MS) in the suspension vehicles significantly reduced with increasing concentration of Vehicle 1 and/or Vehicle 2 (Fig. 1) in comparison to its water solubility. During one month storage of MS microparticles in selected suspension vehicles, the MS leakage from microparticles into the liquid vehicle did not exceed 1.7 % of dose (Tab. 1). The dissolution profiles after one month of suspension storage in different vehicles were similar to the initial profile (similarity factor > 62% for all profiles, Fig. 2). Conclusion Redispersible multi-dose suspensions based on coated metoprolol succinate sustained-release microparticles were developed. After one month storage at room temperature, there was negligible leakage of drug into any of the vehicle compositions tested and, regardless of vehicle choice, the sustained release profile of metoprolol did not significantly change upon storage.
Original languageEnglish
Pages1
Number of pages1
Publication statusPublished - 07 Nov 2018
Externally publishedYes
EventAAPS PharmSci360 - Walter E. Washington Convention Center, Washington, DC, United States
Duration: 04 Nov 201807 Nov 2018
https://www.aaps.org/pharmsci/annual-meeting

Conference

ConferenceAAPS PharmSci360
CountryUnited States
CityWashington, DC
Period04/11/201807/11/2018
Internet address

Fingerprint

Dive into the research topics of 'A patient-centric approach: Formulation of prolonged release microparticles to be used in oral suspensions for older patients with dysphagia'. Together they form a unique fingerprint.

Cite this