Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance

An Electronic Tongue: Evaluation of the Masking Efficacy of Sweetening and/or Flavoring Agents on the Bitter Taste of Epinephrine

An epinephrine (E) tablet is under development for sublingual (SL) administration for the first-aid treatment of anaphylaxis; however, the inherent bitterness of E may hinder acceptability by patients, especially children. To assess the degree of E bitterness and to predict the masking effects of sweetening and/or flavoring non-medicinal ingredients (NMIs), the potential usefulness of an electronic tongue (e-Tongue) was evaluated. The e-Tongue sensors were conditioned, calibrated, and tested for taste discrimination. Six standard active pharmaceutical ingredients were used to build and validate a bitterness model which was then used to assess E bitartrate (EB) solutions from 0.3–9 mM. Taste-masking efficiency of aspartame (ASP), acesulfame potassium (ASK), and citric acid (CA) each at 0.5 mM was evaluated. Using EB 9 mM, the bitterness score was 20 on a scale of 20 (unacceptable) down to 1 (not detected). When NMIs 0.5 mM were added, neither ASK (17.2, unacceptable) nor was ASP (14.0, limit acceptable) effective in masking the bitter taste. When the combination of ASK and ASP was used, the bitterness score was reduced to 9.2 (acceptable). However, the addition of CA alone resulted in the best reduction of the bitterness score to 3.3 (not detected). Using the e-Tongue, the incorporation of a variety of sweetening and/or flavoring NMIs into a SL tablet of E could be shown to mask its bitter taste by up to 80%. These results should be confirmed by in vivo studies

Development of a Mini-Tablet of Co-Grinded Prednisone–Neusilin Complex for Pediatric Use

The purpose of this study is to enhance the dissolution rate of prednisone by co-grinding with Neusilin to form a complex that can be incorporated into a mini-tablet formulation for pediatrics. Prednisone–Neusilin complex was co-grinded at various ratios (1:1, 1:3, 1:5, and 1:7). The physicochemical properties of the complex were characterized by various analytical techniques including: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), particle size, surface area, solubility, and dissolution rate. The co-grinded prednisone–Neusilin complex (1:7) was blended with other excipients and was formulated into a 2-mm diameter mini-tablet. The mini-tablets were further evaluated for thickness, weight, content uniformity, and dissolution rate. To improve taste masking and stability, mini-tablets were coated by dip coating with Eudragit® EPO solution. DSC and XRPD results showed that prednisone was transformed from crystalline state into amorphous state after co-grinding with Neusilin. Particle size, surface area, and SEM results confirmed that prednisone was adsorbed to Neusilin’s surface. Co-grinded prednisone–Neusilin complex (1:7) had a solubility of 0.24 mg/mL and 90% dissolved within 20 min as compared to crystalline prednisone which had a solubility of 0.117 mg/mL and 30% dissolved within 20 min. The mini-tablets containing co-grinded prednisone–Neusilin complex (1:7) exhibited acceptable physicochemical and mechanical properties including dissolution rate enhancement. These mini-tablets were successfully dip coated in Eudragit® EPO solution to mask the taste of the drug during swallowing. This work illustrates the potential use of co-grinded prednisone–Neusilin to enhance solubility and dissolution rate as well as incorporation into a mini-tablet formulation for pediatric use

Dental Mold: A Novel Formulation to Treat Common Dental Disorders

Oral administration of antibiotics to treat dental problems mostly yields slow actions due to slow onset and hepatic “first-pass.” Again, commonly used dental paints are generally washed out by saliva within few hours of application. To overcome the challenges, polymeric molds to be placed on an affected tooth (during carries and gum problems) were prepared and evaluated in vitro for sustained drug release for prolonged local action. Here, amoxicillin trihydrate and lidocaine hydrochloride were used as model drugs. Dental molds were prepared using corn zein, carbopol 934 P, gum karaya powder, and poloxamer 407 by mixing and solvent evaporation technique. Different physicochemical evaluation studies such as tooth adhesion test, surface pH, swelling index, and drug-distribution pattern were carried out. Percentage swelling varied from 56% to 93%. Average tooth adhesion strength and mean initial surface pH of the formulations were 50 g and 6.5, respectively. As assessed by scanning electron microscopy, drug distribution was uniform throughout the matrix. Cumulative percentage release of lidocaine hydrochloride and amoxicillin trihydrate in simulated saliva were 98% and 50%, respectively. In vitro drug-release studies revealed the sustained-release patterns of the drugs in simulated saliva at least for 24 h. The stability study shows that the drugs were stable in the formulations following the conditions as per ICH guideline. The formulation is a novel approach to deliver the drug(s) for a prolonged period for local action upon its application on an affected tooth