Paul W.S.Heng

GEA-NUS Pharmaceutical Processing Research Laboratory,Department of Pharmacy,National University of Singapore,18 Science Drive 4,Singapore 117543

Compaction of coated multi-particulates

Paul W.S.Heng*

GEA-NUS Pharmaceutical Processing Research Laboratory,Department of Pharmacy,National University of Singapore,18 Science Drive 4,Singapore 117543

A R T I C L E I N F O

Article history:

Available online 28 October 2015

Coated multi-particulates

Controlled release solid dosage

forms

There has been a strong interest for controlled release solid dosage forms,and to achieve controlled release,coating of particulates is often attempted to modify drug release.Due to the disadvantages of coated single-unit dosage forms,such as occurrences of dose dumping and local irritation,coated multiparticulates are often preferred.However,coated multiparticulates are often flled into capsules.Compressed tablet dosage form is more desirable than capsules as the unit production costs of tablets are lower and tablet presses are more common.The avoidance of gelatin is another impetus.Compaction of multi-particulates into tablets can also allow dosing fexibility as tablets may be scored.However,compaction forces can result in structural damage to coatings,affecting their function.Hence,it is important to understand the factors that can affect coat damage during compression,requiring research into the various aspects of compacting coated multi-particulates, from the coating process,coat quality,nature of cores,accompanying ingredients,tooling type,and process of force application among others.The structural damage during compression may be reduced by using smaller particles[1],but coating small particles is challenging[2].Thus,judicious selection and optimization of the fuid bed coating process are important.It is also necessary to examine the impact of compacting coated particles with commonly used excipients,often necessitate the design of sacrifcial granules to mitigate the harsh conditions required for the formation of compacts in a die of the tablet press[3,4].Excipients with smaller mean particle size could reduce the coat damage of multi-particulates during compression[5].However,even with the usage of the fnest grade of lactose,the drug release was about 3 times faster than the uncompressed coated particles.Besides excipient properties,the size of the coated particles could have also contributed to the failure of coat function after compression. It is also of interest to explore the use of smaller coated particles for compression.Nevertheless,the coating of small particles has always been a challenge due to the propensity of small particles to agglomerate[6].

In order to reduce the amount of agglomeration,the spray rate of the coating media needed to be reduced.However,reducing spray rate increased the level of spray drying,resultingin signifcant loss of coating material.In addition,coat quality could be affected when coating is applied in very dry coating conditions.Thus,understanding and optimizing the coating process to determine the ideal coating parameters for coating small particles is very important.Application of a side spray onto a swirling fow of particulates is very successful for coating small particles[7],and a high spray rate with minimal agglomeration can be achieved for pellets in the low few hundred microns size range.Careful application of the compaction force onto coated multi-particulates could also help to mitigate the extent of coat damage during the compaction.This can be achieved by the use of air compensator to limit the applied force and extend compaction dwell time.This presentation will examine the various factors involved in the preparation and compaction of coated multi-particulates,highlighting the various research studies carried out in this area.

R E F E R E N C E S

[1]Heng PWS,Chan LW,Liew CV,et al.Effect of tabletting compaction pressure on alginate microspheres.J Microencapsul 2000;17:553–564.

[2]Wang L,Heng PWS,Liew CV.Cluster formation and drag reduction–proposed mechanism of particle recirculation within the partition column of the bottom spray fuid-bed coater.J Pharm Sci 2015;104(4):1303–1310.

[3]Lin X,Chin WC,Ruan KF,et al.Development of potential novel cushioning agents for the compaction of coated multi-particulates by co-processing micronized lactose with polymers.Eur J Pharm Biopharm 2011;79(2):406–415.

[4]Li XH,Xu DS,Li M,et al.Preparation of co-spray dried cushioning agent containing stearic acid for protecting pellet coatings when compressed.Drug Dev Ind Pharm 2015;in press.

[5]Chin WC,Chan LW,Heng PWS.A mechanistic investigation on the utilization of lactose as a protective agent for multi-unit pellet systems.Pharm Dev Technol 2014;doi:10 .3109/10837450.2014.991875.

[6]Wong PM,Chan LW,Heng PWS.Investigation on side spray fuidized bed granulation with swirling airfow.AAPS PharmSciTech 2013;14(1):211–221.

[7]Xu M,Heng PWS,Liew CV.Evaluation of coat uniformity and taste-masking effciency of irregular-shaped drug particles coated in a modifed tangential spray fuidized bed processor. Exp Opin Drug Deliv 2015;12(10):1597–1606.doi:10.1517/ 17425247.2015.1054278.

*E-mail address:paulheng@nus.edu.sg.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.010

1818-0876/?2016 The Author.Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).