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Preformulation investigations into the development of drug formulations, encompassing considerations related to the structure of the drug, excipients, composition, and physical attributes are crucial. This phase is pivotal in ensuring the ultimate success of nanoemulsion development. The objective of this study was to evaluate and define the properties of bedaquiline (BDQ) and the necessary excipients for the formulation of self-emulsifying BDQ-loaded nanoemulsions. To determine the saturation solubility of BDQ in various oils, an in-house validated HPLC method was used. Fourier transform infrared spectroscopy was utilised to identify and evaluate the compatibility between BDQ and the selected excipients. The water titration method was used to construct phase diagrams to identify the type of structure that resulted following emulsification and to characterise the behaviour of mixtures along dilution paths. The solubility studies revealed that BDQ exhibited the highest solubility in olive oil, with a solubility of 3.45 ± 0.041 mg/ml. The design space led to the formation of emulsions categorised as Winsor products. Importantly, the FTIR data indicated the absence of any potential interactions between BDQ and the chosen excipients. The preformulation studies were successful and facilitated the selection of compatible and suitable excipients for the formulation of BDQ-loaded nanoemulsions.

Background: Pharmacy professionals working in community pharmacies frequently provide pharmacist-initiated therapy, including codeine-containing medicines. Codeine is an opioid with great potential for misuse, adding to the global opioid epidemic burden. Professional pharmacy personnel are the first intervention point in relation to management of codeine use. This study highlights the importance of pharmacy professionals’ perceptions and behaviours in combatting the opioid epidemic. Methods: A descriptive cross-sectional study was conducted. Simple random sampling included pharmacy professionals in the metropolitan city of Johannesburg. An electronic questionnaire was distributed via e-mail and data analysed descriptively. Results: Findings indicate that pharmacy personnel routinely ask patients about codeine use (n = 48; 53.9%), avoid dispensing over-the-counter (OTC) codeine as an initial treatment (n = 61; 69%) and express confidence to identify and manage codeine misuse (n = 69; 77.5%). Despite this, increased patient demands for OTC codeine (n = 69; 77.5%) were concerning, highlighting the ease of availability from internet sources (n = 76; 85.4%) and multiple pharmacies (n = 84; 94.4%). Apprehension about the lack of patient awareness on adverse health consequences (n = 66; 74.2%) and the risk of codeine dependence (n = 79; 88.8%) was expressed. Conclusion: Growing concern regarding availability and accessibility of codeine-containing medicines within the community pharmacy sector is highlighted. Adverse health consequences of codeine misuse and dependence are not understood by customers and the ineffective information provided by pharmacy personnel was highlighted as a concern. Contribution: The results of this study give insight to the influence of dispensing personnel’s attitude towards the growing challenges with respect to codeine containing medication abuse.

Abstract Treatment of severe lower extremity trauma, diabetic complications, infections, dysvascular limbs, neoplasia, developmental pathology, or other conditions often involves amputation of the involved extremity. However, techniques of lower extremity amputation have largely remained stagnant over decades. This article reports a reproducible technique for transtibial osteomyoplastic amputation.

Four previously unreported triterpenoid saponins named 3β-hydroxy-23-oxours-12-en-28-oic acid 28-O-β-D-glucopyranosyl ester (mannioside G) (1), 23-O-acetyl-3β-hydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranosyl ester (mannioside H) (2), ursolic acid 28-O-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester (mannioside I) (3), and 3β-hydroxy-23-oxolup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (mannioside J) (4) were isolated as minor constituents from the EtOAc soluble fraction of the MeOH extract of the leaves of Schefflera mannii along with the known compounds 23-hydroxyursolic acid 28-O-β-D-glucopyranosyl ester (5), ursolic acid 28-O-β-D-glucopyranosyl ester (6), pulsatimmoside B (7) betulinic acid 28-O-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester (8), 23-hydroxy-3-oxo-urs-12-en-28-oic acid (9), hederagenin (10), ursolic acid (11), betulinic acid (12), and lupeol (13). Their structures were elucidated by a combination of 1D and 2D NMR analysis and mass spectrometry. The MeOH extract, the EtOAc and n-BuOH fractions, and some of the isolated compounds were evaluated for their antibacterial activity against four bacteria: Staphylococcus aureus ATCC1026, Staphylococcus epidermidis ATCC 35984, Escherichia coli ATCC10536, and Klepsiella pnemoniae ATCC13882. They were also screened for their antioxidant properties, but no significant results were obtained.

Paediatric Tuberculosis (TB) continues to be a major global cause of morbidity and mortality. Children are more prone to contracting TB, which can spread quickly to extrapulmonary infection sites. Although the pathophysiology of the disease, drug pharmacokinetics, and the therapeutic window in children differ from those of adults, the same drugs used to treat adult TB have long been utilised to treat paediatric TB infections. Since many current formulations such as tablets are unsuitable for children due to difficulty swallowing and risk of choking, adult medications are frequently used by breaking or crushing tablets to obtain a paediatric dose. This can result in inaccurate dosing due to pharmacokinetic differences in children which could subsequently lead to sub-therapeutic or toxic systemic concentrations. In addition, many of the medications used in the treatment of TB and most medicines in general, have a profoundly unpleasant taste to children causing them to reject and spit out medication which contributes to challenges with adherence, ultimately leading to treatment failure. The aforementioned demonstrates a huge need for the development of novel drug delivery formulations that are paediatric-friendly and address the limitations of current dosage forms. This review discusses the currently available oral paediatric formulations, recent developments of novel oral drug delivery systems studied to overcome the current problems associated with the treatment of tuberculosis in paediatrics and provides potential direction for future research through nanotechnology by using a SWOT analysis.

Bedaquiline (BDQ) is a drug used to treat multidrug‐resistant tuberculosis (MDR‐TB). It exhibits exposure‐dependent efficacy in eliminating Mycobacterium tuberculosis (Mtb). An easy, efficient and precise reverse‐phase ultrafast liquid chromatography (RP‐UFLC) method was developed to validate the free base of the antitubercular medication BDQ. BDQ was separated using a 10:90 v/v mobile phase of ammonium acetate buffer solution (pH = 5.4) and high‐performance liquid chromatography–grade methanol, with a flow rate of 1.5 mL/min and a UV detection wavelength of 226 nm. By using the Box–Behnken design (BBD) and response surface methodology (RSM), the method was optimised by varying critical analytical attributes (CAA) and critical performance attributes (CPAs) namely ammonium acetate fraction (%), flow rate (ml/min), buffer system molarity (M) and pH. BDQ was eluted at 7.5 min utilising isocratic elution. The method was linear in the concentration range of 0.5–300 μg/mL with limit of detection values of 0.039 μg/mL and limit of quantification of 0.12 μg/mL. The results indicate that this validated method can be used as an alternative method for assay of BDQ. [ABSTRACT FROM AUTHOR]

Cordyline species have a long history in traditional medicine as a basis of treatment for various ailments such as a bloody cough, dysentery, and a high fever. There are about 26 accepted species names in this genus distributed worldwide, including C. fruticosa, C. autralis, C. stricta, C. cannifolia, and C. dracaenosides. This work presents a comprehensive review of the traditional uses of plants of the genus Cordylie and their chemical constituents and biological activities. A bibliographic search was conducted to identify available information on ethnobotany, ethnopharmacology, chemical composition, and biological activities. A total of 98 isolated compounds potentially responsible for most of the traditional medicinal applications have been reported from eight species of Cordyline and are characterised as flavonoid, spirostane, furostane, and cholestane glycosides. Some of these pure compounds, as well as extracts from some species of Cordyline, have exhibited noteworthy anti-oxidant, antiproliferative, antimicrobial, and hypolipidemic activities. Although many of these species have not yet been investigated phytochemically or pharmacologically, they remain a potential source of new bioactive compounds.

Objective. Little is known concerning chronic obstructive pulmonary disease (COPD) in Sub-Saharan Africa (SSA), where the disease remains underdiagnosed. We aimed to estimate its prevalence in Cameroon and look for its predictors. Methods. Adults aged 19 years and older were randomly selected in 4 regions of Cameroon to participate in a cross-sectional community-based study. Data were collected in the participant’s home or place of work. Spirometry was performed on selected participants. COPD was defined as the postbronchodilator forced expiratory volume in 1 second/forced vital capacity ratio FEV1/FVC

Maltitol (MAL) is a well-known polyol with potential pharmaceutical applications. Unlike other polyols, its utilization as a carrier for solid dispersions (SDs) has not been adequately investigated. This research studied the feasibility of MAL as an SD carrier to enhance the biopharmaceutical properties of a BCS class I/III drug, isoniazid (INH). SDs of INH–MAL were prepared by the fusion method, and physicochemical characteristics were investigated to determine the solid-state habit, solubility and permeation enhancement of INH. Fourier-transform infrared (FT-IR) spectroscopy demonstrated significant peak broadening for the SDs consisting of a higher MAL concentration. Powder X-ray diffraction indicated a decrease in degree of crystallinity with increasing MAL concentration. Hot-stage microscopy (HSM) and scanning electron microscopy (SEM) revealed that INH–MAL molar ratios affect the type of SD prepared via the fusion method. Results from the equilibrium solubility studies indicated significant INH solubility improvement (p < 0.05) with SDs in comparison with the pure drug and physical mixtures. The artificial membrane permeation assay (PAMPA) of INH was positively affected by the presence of MAL. The results of the study indicated the potential for MAL as a carrier in the preparation of SDs for the solubility and/or permeability enhancement of drugs.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21β-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc–14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21β-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 μg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 μg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 μg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 μg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21β-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21β-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

Crystalline carriers such as dextrose, sucrose, galactose, mannitol, sorbitol, and isomalt have been reported to increase the solubility, and dissolution rates of poorly soluble drugs when employed as carriers in solid dispersions (SDs). However, synthetic polymers dominate the preparation of drugs: excipient SDs have been created in recent years, but these polymer-based SDs exhibit the major drawback of recrystallisation upon storage. Also, the use of high-molecular-weight polymers with increased chain lengths brings forth problems such as increased viscosity and unnecessary bulkiness in the resulting dosage form. An ideal SD carrier should be hydrophilic, non-hygroscopic, have high hydrogen-bonding propensity, have a high glass transition temperature (Tg), and be safe to use. This review discusses sugars and polyols as suitable carriers for SDs, as they possess several ideal characteristics. Recently, the use of low-molecular-weight excipients has gained much interest in developing SDs. However, there are limited options available for safe, low molecular excipients, which opens the door again for sugars and polyols. The major points of this review focus on the successes and failures of employing sugars and polyols in the preparation of SDs in the past, recent advances, and potential future applications for the solubility enhancement of poorly water-soluble drugs.

Abstract Background Spirometric reference values are well known in several ethnic groups but the normative spirometric values of blacks living in Africa have been less studied. The purpose of this study is to establish normative spirometric equations from a representative population of Cameroonian children and adults and compare these equations with those developed by the Global Lung Initiative (GLI) and in Nigerians. Methods Spirometric data from healthy Cameroonians aged 4–89 years randomly collected between 2014 and 2018 were used to derive reference equations using generalized additive model for location (mu), shape (lambda) and scale (sigma). Results A total of 625 children and adolescents (290 males and 335 females) and 1152 adults (552 males and 600 females) were included in the study. The prediction equation for spirometric index was written as: M = Exp[a0 + a1*ln (Height) + a2*ln (Age) + Mspline, Mspline was age related spline contribution]. Applying the GLI standards for African Americans resulted in overall values greater than those found in our study for forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). These values were very close in children and adolescents while the values obtained with the GLI equations for African Americans were significantly higher in adults. FEV1/FVC ratio in our study was similar for adult males but lower in adult females (88% vs 85%, difference = + 3.5%) when applying Nigerian standards. Conclusions FEV1 and FVC of the Cameroonian infant and adolescent population are very close to those of black Americans. However, FEV1 and FVC of Cameroonian adults are significantly lower than those of black American adults. These equations should allow a more suitable interpretation of spirometry in the Cameroonian population.