Sublimation of Drugs from the Site of Application of Topical Products

Abstract

The objective of the project was to investigate the plausibility of active pharmaceutical ingredients (APIs) to undergo sublimation from topical application following evaporation of solvent. Topical formulations with different APIs were subjected to a sublimation screening test. The APIs in the selected topical products were found to undergo sublimation to a different extent. The salicylic acid topical product was found to undergo a significant loss due to sublimation. The extent of sublimation of salicylic acid was significantly greater at skin temperature compared to room temperature. When the APIs were subjected to the sublimation screening test in their neat form at 32 ± 1 °C, the natural log of the rate of sublimation decreased linearly with the standard enthalpy of sublimation of compound (R 2 = 0.89). The formulation composition was found to have a significant impact on the extent of sublimation of the representative API, salicylic acid. The sublimation of APIs from the topical product was found to affect the mass balance studies in the case of the salicylic acid ointment. Furthermore, the results of the human studies agreed with the in vitro experimental results demonstrating the plausibility of loss of API due to sublimation from the site of application.

Novel Gastroprotective and Thermostable Cocrystal of Dimethyl Fumarate: Its Preparation, Characterization, and In Vitro and In Vivo Evaluation

“…Therefore, the DF–NIC cocrystal can prevent the sublimation of neat DF during manufacturing and storage and increase its long-term stability, thus making the drug development economic and sustainable. There are other drugs also which are prone to loss due to sublimation, like salicylic acid, in which there is significant loss from the site of application . However, cocrystals have been prepared to prevent the loss due to sublimation by shielding the API …”

“…There are other drugs also which are prone to loss due to sublimation, like salicylic acid, in which there is significant loss from the site of application. 35 However, cocrystals have been prepared to prevent the loss due to sublimation by shielding the API. 36 Effect of Cocrystallization on the Dissolution Profile.…”

Controlled Sublimation Rate of Guest Drug from Polymorphic Forms of a Cyclodextrin-Based Polypseudorotaxane Complex and Its Correlation with Molecular Dynamics as Probed by Solid-State NMR

“…25,26 A recent study by Murthy and coworkers demonstrated that SA suffers significant weight loss at skin temperature (32 °C) by sublimation due to its high vapor pressure from its crystalline state as well as topical formulations. 27 The physical stability issues related to the high vapor pressure of APIs have been addressed by cocrystal/ salt formation or complexation with CDs. 28−32 Herein, we investigated the sublimation suppression of SA from the three polymorphic forms of the SA/(PEG/γ-CD-PPRX) complex, which were prepared by the previously reported sealed-heating technique.…”

“…In this study, salicylic acid (SA) was selected as the model drug. SA is typically used in topical formulations to treat chronic skin diseases for its keratolytic, anti-inflammatory, and bacteriostatic properties. , A recent study by Murthy and co-workers demonstrated that SA suffers significant weight loss at skin temperature (32 °C) by sublimation due to its high vapor pressure from its crystalline state as well as topical formulations . The physical stability issues related to the high vapor pressure of APIs have been addressed by cocrystal/salt formation or complexation with CDs. − Herein, we investigated the sublimation suppression of SA from the three polymorphic forms of the SA/(PEG/γ-CD-PPRX) complex, which were prepared by the previously reported sealed-heating technique. , The sublimation rate of SA was determined by thermogravimetry under isothermal conditions.…”