Hot Melt Coating of Amorphous Carvedilol

Abstract

The use of amorphous drug delivery systems is an attractive approach to improve the bioavailability of low molecular weight drug candidates that suffer from poor aqueous solubility. However, the pharmaceutical performance of many neat amorphous drugs is compromised by their tendency for recrystallization during storage and lumping upon dissolution, which may be improved by the application of coatings on amorphous surfaces. In this study, hot melt coating (HMC) as a solvent-free coating method was utilized to coat amorphous carvedilol (CRV) particles with tripalmitin containing 10% (w/w) and 20% (w/w) of polysorbate 65 (PS65) in a fluid bed coater. Lipid coated amorphous particles were assessed in terms of their physical stability during storage and their drug release during dynamic in vitro lipolysis. The release of CRV during in vitro lipolysis was shown to be mainly dependent on the PS65 concentration in the coating layer, with a PS65 concentration of 20% (w/w) resulting in an immediate release profile. The physical stability of the amorphous CRV core, however, was negatively affected by the lipid coating, resulting in the recrystallization of CRV at the interface between the crystalline lipid layer and the amorphous drug core. Our study demonstrated the feasibility of lipid spray coating of amorphous CRV as a strategy to modify the drug release from amorphous systems but at the same time highlights the importance of surface-mediated processes for the physical stability of the amorphous form.

Amorphous Form of Carvedilol Phosphate—The Case of Divergent Properties

“…The obtained results determined the melting point for CVD in the crystalline form at 160.5 • C (Figure 2). According to previous literature reports, the Thermogram of the amorphous form did not show the melting transition and showed a broad endothermic peak at 46.4 • C, corresponding to its glass transition temperature (Figure 2) [35][36][37][38]. This result confirms the complete amorphization process for the selected methodology and the relatively low humidity of the samples [39], which is extremely important for the amorphous form due to the induction of the recrystallization process by water molecules [40].…”

Amorphous Drug-Polymer Salts

“…Besides polyelectrolyte coatings, other coating methods have been used to improve the properties of amorphous formulations, both solvent-based [ 44 , 45 , 46 , 47 , 48 ] and solvent-free [ 39 , 49 , 50 , 51 , 52 ]. Relative to the other methods, polyelectrolyte coatings applied via electrostatic deposition are characterized by extremely small thickness (several to tens of nanometers per layer).…”

Dry-Coating of Powder Particles is Current Trend in Pharmaceutical Field

“…Situations calls for HMC are elimination for use of aqua or non-aqua solvents, enhancing solubility and dissolution rate of poorly aqua-soluble drug, enhancing chemical stability of moisture sensitive drugs, and many more [27][28][29] . An absence of solvent evaporation phase results strong and nonporous particles 2,3,27,30 .…”

“…In this process, as the name implies, meltable CoM, in the molten state, is applied onto substrate particle that solidifies upon cooling. The process uses meltable CoMs with low melting point, usually lipid or waxes [30][31][32][33] . The process requirement is the meltable CoMs had to be heated to molten state for having their solution that then air-atomised and sprayed onto surface of moving solid substrate followed by cooling of the product 30,32,33 .…”