Pharmaceutical approaches for enhancing solubility and oral bioavailability of poorly soluble drugs.

High solubility in water and physiological fluids is an indispensable requirement for the pharmacological efficacy of an active pharmaceutical ingredient. Indeed, it is well established that pharmaceutical substances exhibiting limited solubility in water are inclined towards diminished and inconsistent absorption following oral administration, consequently resulting in variability in therapeutic outcomes. The current advancements in combinatorial chemistry and pharmaceutical design have facilitated the creation of drug candidates characterized by increased lipophilicity, elevated molecular size, and reduced aqueous solubility. Undoubtedly, the issue of poorly water-soluble medications has been progressively escalating over recent years. Indeed, 40% of the top 200 oral medications marketed in the United States, 33% of drugs listed in the US pharmacopoeia, 75% of compounds under development and 90% of new chemical entities are insufficiently water-soluble compounds. In order to address this obstacle, formulation scientists employ a variety of approaches, encompassing both physical and chemical methods such as prodrug synthesis, salt formation, solid dispersions formation, hydrotropic substances utilization, solubilizing agents incorporation, cosolvent addition, polymorphism exploration, cocrystal creation, cyclodextrins complexation, lipid formulations, particle size reduction and nanoformulation techniques. Despite the utilization of these diverse approaches, the primary reason for the failure in new drug development persists as the poor aqueous solubility of pharmaceutical compounds. This paper, therefore, delves into the foundational principles that underpin the implementation of various formulation strategies, along with a discussion on the respective advantages and drawbacks associated with each approach. Additionally, a discourse is provided regarding methodological frameworks for making informed decisions on selecting an appropriate formulation strategy to effectively tackle the key challenges posed during the development of a poorly water-soluble drug candidate.

Determinants and prevalence of symptomatic dengue fever among adults in the Central Region of Burkina Faso: a hospital-based cross-sectional study.

BACKGROUND: Dengue fever (DF) is a significant public health concern in Burkina Faso, particularly in the Central Region, previously endemic for malaria. However, limited research has focused on dengue prevalence and associated factors among adult febrile patients in this region. This study aimed to estimate the prevalence of symptomatic dengue fever among adults and identify the sociodemographic and clinical determinants of the disease. METHODS: A seroepidemiological cross-sectional study was conducted in the Central Region of Burkina Faso, through a three-stage sampling. Five health facilities, one from each of the region five districts, were purposively selected. Febrile patients aged 16 and older, suspected of having dengue, were included in the study, after consenting. Bivariate analyses and multivariate binary logistic regression were done at a 5% confidence level. RESULTS: A total of 637 patients between the ages of 16 and 90 years were included. Most of the participants were females (58.71%). Most dengue cases resided in Arrondissement 4 (59.62%), or were present in the Arrondissement 4 at daytime during the previous days (51.92%). 52.90% of the participants knew of dengue. Dengue prevalence was estimated at 8.16% (95% CI: 6.16%-10.57%). The most frequent markers for dengue were immunoglobulins M detected in 4.40% (2.94%-6.29%), followed by Antigen NS1 at 4.24% (95% CI: 2.81%-6.11%). The Antigen NS1 marker was associated with myalgia (p = 0.024), vomiting (p < 0.001), hemorrhagic manifestations (p = 0.001), and anorexia (p < 0.001). Staying at Arrondissement 4 (vs staying at Saaba) during daytime (aOR = 2.36 95% CI: 1.03-5.45; p = 0.044) significantly increased the odds of dengue. Dengue cases were about 3 times more likely to have vomited (aOR = 2.99 95% CI: 1.58-5.64; p = 0.001). Participants knowing of dengue (aOR = 0.53 95% CI: 0.29-0.98; p = 0.042) and those coinfected with malaria (aOR = 0.28 95% CI: 0.14-0.57; p < 0.001) instead had reduced odds of dengue. CONCLUSION: The study revealed a relatively high prevalence of symptomatic dengue fever among adults in the Central Region of Burkina Faso in 2022. These findings emphasize the need for continuous surveillance and targeted control measures. The low coinfection of dengue and malaria warrants further investigation.

Setting Dengue Fever Epidemic Thresholds Between 2016 and 2021 in the Central Health Region, Burkina Faso: An Ecological Study.

BACKGROUND: Dengue fever (DF) is endemic in Burkina Faso, with 70% of its burden supported by the Central Health Region. Then, a single confirmed case can no longer mean an epidemic. This study aimed at describing trends and setting epidemic thresholds of DF in the Central Health Region. DATA AND METHODS: An ecological study was conducted using monthly data from DF surveillance between 2016 and 2021. Three methods were applied to set alert and intervention thresholds of DF monthly incidence rate: mean [mean + 2 SD], median [3rd quartile] and cumulative sum (C-sum) [C-sum + 1.96 SD]. These thresholds were plotted with the monthly incidence rates for 2021. RESULTS: In total, 54,429 cases were reported between 2016 and 2021. Dengue cases increased biannually. The median annual incidence rate did not vary significantly across years [Kruskal-Wallis: χ2(5) = 9.825; p = 0.0803]. Within a year, the monthly incidence rate fell under 48.91 cases per 100,000 inhabitants between January and September and peaked in October or November. With the mean and C-sum methods, the 2021 monthly incidence rate remained below the intervention thresholds (Mean + 2 SD and C-sum + 1.96 SD). With the median method, the incidence rate exceeded the alert and intervention thresholds in July-September 2021. CONCLUSIONS: If the DF incidence varied within a year due to the seasons, it was relatively stable between 2016 and 2021. The mean and C-sum methods based on the mean were subject to extreme values, giving high thresholds. The median method seemed better for capturing the abnormal increase in dengue incidence.

Hospital preparations of ethanol-free furosemide oral solutions: Formulation and stability study.

Furosemide is a diuretic frequently used in the therapeutic management of edema associated with cardiac, renal, and hepatic failure and hypertension. However, there are a very low number of pharmaceutical dosage forms containing furosemide that are suitable for children under 6- years old. Therefore, there is a real need to develop hospital preparations, especially in the hospital. Four oral pediatric solutions of furosemide (2 mg/Ml) were formulated. Two of those solutions did not contain ethanol. For each formulation, 12 batches of 1600.0 Ml were prepared and packaged in 250.0 Ml brown glass bottles with polypropylene screw caps. The physicochemical properties (visual appearance, pH, osmolarity, drug content) and microbiological quality of the finished product were determined on the freshly prepared solutions and after 90 days of storage at 30°C/65% RH. The physicochemical and microbiological characteristics of the freshly prepared solutions were within the prescribed specifications. After 90 days of storage at 30°C/65% RH, the solutions containing sucrose and those without ethanol showed a slight decrease in pH and furosemide content of about 2.5%-4.5% (w/w). Despite this slight decrease, the characteristics remained within the prescribed specifications. Based on the stability profile of the ethanol-free solution containing sorbitol, it could be implemented in hospitals for the care of pediatric patients.

Preclinical Evaluation of the Antihypertensive Effect of an Aqueous Extract of Anogeissus leiocarpa (DC) Guill et Perr. Bark of Trunk in L-NAME-Induced Hypertensive Rat.

BACKGROUND: The present study investigates the effect of an aqueous extract of Anogeissus leiocarpa (AEAL) on normotensive Wistar rats and its chronic antihypertensive effects in L-NAME-induced hypertensive rats by using a non-invasive tail-cuff model. METHODS: The effects of AEAL (50mg/kg) and NaCl 0.9% on blood pressure were investigated by daily oral administration in normotensive Wistar rats over four weeks. L-NAME-induced hypertensive rats were produced by L-NAME (40mg/kg) daily oral administration for two weeks. For chronic antihypertensive effects, induced hypertensive rats have received L-NAME in combination with AEAL (10 or 50mg/kg/day) for two following weeks. RESULTS: In normotensive rats, daily administration of AEAL (50mg/kg) has no significant effect on their blood pressure, which was similar to that of the control group. L-NAME's daily oral administration induces a progressive increase in systolic blood pressure (SBP) from 115.8 ± 7.9mmHg to 153.5 ± 4.6mmHg after two weeks, which was maintained to the end of the treatment. In L-NAME-induced hypertensive rats, AEAL (50mg/kg/day) significantly decreases the SPB from 160.0 ± 5.8 mmHg to 108.8 ± 2.7mmHg after only four days of administration. However, the lower dose of AEAL (10mg/kg) also normalized the SBP of L-NAME-induced hypertensive rats but only evident after seven days of administration. Moreover, AEAL does not effect on the serum biochemical parameters (ALAT, ASAT, CREAT, etc.) and any macroscopic adverse effect was detected on the sensible organs involved during hypertension. In the aorta rings from treated rats, AEAL (50mg/kg/day) alone or in combination with L-NAME has enhanced the vasodilation effect of acetylcholine. However, the vasodilation effect of AEAL alone or in association with L-NAME has enhanced the sodium nitroprusside effect in treated rat aorta rings after autopsy. CONCLUSION: These findings suggest that AEAL affords significant antihypertensive effects against L-NAME-induced hypertensive rats without modification of serum parameters and deleterious effects.