Convection-Induced vs. Microwave Radiation-Induced in situ Drug Amorphization

Abstract

The aim of the study was to investigate the suitability of a convection oven to induce in situ amorphization. The study was conducted using microwave radiation-induced in situ amorphization as reference, as it has recently been shown to enable the preparation of a fully (100%) amorphous solid dispersion of celecoxib (CCX) in polyvinylpyrrolidone (PVP) after 10 min of continuous microwaving. For comparison, the experimental setup of the microwave-induced method was mimicked for the convection-induced method. Compacts containing crystalline CCX and PVP were prepared and either pre-conditioned at 75% relative humidity or kept dry to investigate the effect of sorbed water on the amorphization kinetics. Subsequently, the compacts were heated for 5, 10, 15, 20, or 30 min in the convection oven at 100 °C. The degree of amorphization of CCX in the compacts was subsequently quantified using transmission Raman spectroscopy. Using the convection oven, the maximum degree of amorphization achieved was 96.1% ± 2.1% (n = 3) for the conditioned compacts after 30 min of heating and 14.3% ± 1.4% (n = 3) for the dry compacts after 20 min of heating, respectively. Based on the results from the convection and the microwave oven, it was found that the sorbed water acts as a plasticizer in the conditioned compacts (i.e., increasing molecular mobility), which is advantageous for in situ amorphization in both methods. Since the underlying mechanism of heating between the convection oven and microwave oven differs, it was found that convection-induced in situ amorphization is inferior to microwave radiation-induced in situ amorphization in terms of amorphization kinetics with the present experimental setup.

The Influence of Temperature and Viscosity of Polyethylene Glycol on the Rate of Microwave-Induced In Situ Amorphization of Celecoxib

“…In theory, higher drug loadings than the thermodynamic solubility at room temperature can be made accessible for drug administration using the in situ amorphization approach, as only short-term stability is necessary. Presently, in situ amorphization has been demonstrated by immersion in water, by convectional heating and upon exposure to microwave radiation [1][2][3][4]. Microwave-induced in situ amorphization is based on the absorption of microwave radiation by a dielectric excipient [5].…”

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

“…The enhanced chain flexibility then led to an increase in the molecular mobility of water molecules within the conditioned IND:PVP K12 compacts, which facilitated the molecular friction and heat generation upon microwaving. Moreover, further investigation demonstrated that such a plasticizing effect of water was advantageous not only in microwave-induced in situ amorphization, but also when compacts were exposed to convective heating [85]. It was also suggested that the superiority of PVP K12 in promoting amorphicity could be explained by the fact that PVP K12 was the only polymer in this study possessing a Tg below RT after storage due to the plasticizing effect of water, implying the transformation from glassy to supercooled liquid state occurred with an increased chain flexibility.…”

“…The enhanced chain flexibility then led to an increase in the molecular mobility of water molecules within the conditioned IND:PVP K12 compacts, which facilitated the molecular friction and heat generation upon microwaving. Moreover, further investigation demonstrated that such a plasticizing effect of water was advantageous not only in microwave-induced in situ amorphization, but also when compacts were exposed to convective heating [85].…”

“…The importance of the dissolution of drug in polymer was also addressed by Hempel et al in a comparative study of microwave heating and convective heating to induce in situ amorphization [85]. Two experimental setups were applied in the study, including a microwave-induced method identical to the one that successfully led to 100% CCX amorphicity, as previously described [86], and a comparable convection-induced method that imitated the setup of the former.…”

“…This was primarily due to the fact that the convection heating group exhibited a delayed temperature profile as compared to the microwave heating group arising from their different heating mechanisms, which resulted in a delayed dissolution process of CCX into the PVP and ultimately an incomplete in situ amorphization. The importance of the dissolution of drug in polymer was also addressed by Hempel et al in a comparative study of microwave heating and convective heating to induce in situ amorphization [85]. Two experimental setups were applied in the study, including a microwave-induced method identical to the one that successfully led to 100% CCX amorphicity, as previously described [86], and a comparable convection-induced method that imitated the setup of the former.…”