Application of Hot-Melt Coating Process for Designing a Lipid Based Controlled Release Drug Delivery System for Highly Aqueous Soluble Drugs

Abstract

Hot-melt coating process (HMCP) was applied to develop a lipid based oral controlled release matrix system (tablet) to deliver highly aqueous soluble drugs using paracetamol as a model drug. Granules prepared from paracetamol and particular filler were coated with different levels of lipid and then compressed into tablets to get controlled/sustained delivery of the drug over an optimum period. Process parameters were optimized with particular focus on fluidization pattern during HMCP proposing a 'design space' with 'Quality by Design' (QbD) concept in mind. The results demonstrated that the granule composition influenced the drug release pattern, and the rate of release could be manipulated by varying the amount of lipid in the formulation. The in vitro release profile of the drug was pH-independent and the most promising release profile was obtained from tablets prepared from granules with the water-soluble filler, lactose, and coated at 9% (w/w) level with a lipid, glyceryl behanate. In vivo plasma profiles of the drug were predicted from the in vitro release profile data by convolution analysis which confirmed that the lactose based formulation with 9% (w/w) lipid coating on the granules would be suitable for controlled delivery of the drug over a period of 12 h making the formulation suitable for highly water soluble drug candidates like paracetamol with twice daily dose regimen. Moreover, the dissolution data adequately fitted into Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Theophylline-Loaded Compritol Microspheres Prepared by Ultrasound-Assisted Atomization

“…In particular, solid lipid particles, at micro‐ and/or nano‐scale, possessing matrix made from fatty acids, glycerides, fatty alcohols and solid waxes with high melting point, behave as drug carriers for a controlled as well as sustained drug release, the lipid coating being impermeable to aqueous media and not immediately permeable to the dispersed drug or ready to be dissolved or solubilized. As a consequence, they can be used for protection of the active drug and/or taste masking 4–8…”

Engineering Size and Structure of Particles in Novel Modified-Release Delivery Systems

“…Particles modified by the hot-melt coating process could be not only directly prepared into pellets, but also compacted into tablets or filled into capsules to achieve sustained drug delivery in an optimum period. In a study, the sustained-release tablets were prepared by granules that were made of drug and particular fillers and then coated with different levels of lipid (26). The results showed that the composition of the granule that could be manipulated by changing the amount of lipid in the formulation directly affected the drug release pattern.…”

“…The results showed that the composition of the granule that could be manipulated by changing the amount of lipid in the formulation directly affected the drug release pattern. Thereinto, the granules, containing lactose as matrix and 9% (w/w) glyceryl behanate as coating, were regarded as the ones with the best release profile (26).…”

Influence of Different Meltable Binders on the Solid-State Behaviour and Dissolution Profiles of Solid Lipid Extrudates Processed Via Continuous Hot Melt Granulation

“…Commonly, reported binders such as polyethylene glycol, HPC, HPMC, PEO and HPMC in combination with lipid binders is used in melt granulation [5][6][7]. It has been reported in the literature that polymeric binders are not preferable when granulation process is developed for modified or controlled release applications due to solubility in ethanol and susceptibility to dose dumping in hydroalcoholic media [5][6][7]. To overcome the problem of polymeric meltable binders solid lipids are one ofmost viableoptions.…”