Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax.

The use of lipid-based formulations (LBFs) can be hindered by low dose loading due to solubility limitations of candidate drugs in lipid vehicles. Formation of lipophilic salts through pairing these drugs with a lipophilic counterion has been demonstrated as a potential means to enhance dose loading in LBFs. This study investigated the screening of appropriate counterions to form lipophilic salts of the BCS class IV drug venetoclax. The physical properties, lipid solubility, and in vitro performance of the salts were analyzed. This study illustrated the versatility of alkyl sulfates and sulfonates as suitable counterions in lipophilic salt synthesis with up to ∼9-fold higher solubility in medium- and long-chain LBFs when compared to that of the free base form of venetoclax. All salts formulated as LBFs displayed superior in vitro performance when compared to the free base form of the drug due to the higher initial drug loadings in LBFs and increased affinity for colloidal species. Further, in vitro studies confirmed that venetoclax lipophilic salt forms using alkyl chain counterions demonstrated comparable in vitro performance to venetoclax docusate, thus reducing the potential for laxative effects related to docusate administration. High levels of the initial dose loading of venetoclax lipophilic salts were retained in a molecularly dispersed state during dispersion and digestion of the formulation, while also demonstrating increased levels of saturation in biorelevant media. The findings of this study suggest that alkyl chain sulfates and sulfonates can act as a suitable alternative counterion to docusate, facilitating the selection of counterions that can unlock the potential to formulate venetoclax as an LBF.

Exploring career choices of pharmacy graduates over 15 years: A cross-sectional evaluation.

INTRODUCTION: Career opportunities for pharmacists beyond those commonly associated with the degree continue to emerge. A paucity of literature regarding evaluation of pharmacy graduate career paths over extended periods is apparent. Considering international pharmacy workforce capacity pressures, the primary study aim was to evaluate trends in career paths of pharmacy graduates. METHODS: This study utilised a multimethod approach to access graduate career data using publicly accessible information from LinkedIn® profiles and an online survey. The survey was distributed to all pharmacy graduates of a university (2007-2022). Data from both methods was combined, cross-checked, coded and analysed quantitatively using descriptive and inferential statistics. RESULTS: Data from 69.7% of the university's pharmacy graduates was collected. Community pharmacy was the most prevalent employment sector (47.7%), followed by industry (21.5%) and hospital (17.7%). A higher proportion of more recent graduates (≤5 years post-graduation) work in a community or hospital pharmacy role versus those who graduated greater than five years ago (χ2 = 8.44, df = 2, p < 0.05). Post-graduate education was undertaken by 41.3% of graduates. Career satisfaction was high (88.2%) but was lower (χ2 = 11.31, df = 1, p < 0.05) for those in community and hospital (82%) versus other sectors (97.5%). CONCLUSION: This study provides the first analysis of graduate career paths over an extended period, highlighting a novel approach to track pharmacist workforce. While almost two thirds of pharmacy graduates occupy community or hospital roles, a trend of leaving these settings five years post-graduation was evident. Accordingly, this work represents a springboard for additional research to inform future pharmacist workforce planning worldwide.