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Most evidence on son preference in Pakistan is reflected in the higher child mortality among females than males. The sex discrimination before birth is rarely reported in Pakistan. This is the first study to quantify prenatal sex discrimination in Pakistan on a subnational level. We provide annual estimates of the sex ratio at birth (SRB) from 1980 to 2020 and scenario-based projections of the number of missing female births up to 2050 by Pakistan province. The results are based on a comprehensive database consisting of 832,091 birth records from all available surveys and censuses. We adopted a Bayesian hierarchical time series model to synthesize different data sources. We identified Balochistan with an existing imbalanced SRB since 1980. For the rest provinces without past or ongoing SRB inflation, we projected the largest female birth deficit to occur in Punjab in 2033 under the scenario that the SRB transition process starts in 2021. We demonstrated important disparities in the occurrence and quantification of missing female births up to 2050.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 μg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 μg/min, 399.35 μg/min, and 244.81 μg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.