Capsule-related dysphagia and the use of netupitant/palonosetron (Akynzeo™) capsules – A report of two cases and a solution

Netupitant/palonestron (NEPA, Akynzeo™) is a fixed combination of netupitant 300 mg and palonosetron 0.5 mg that is indicated for the prevention of chemotherapy-induced nausea and vomiting (CINV). NEPA is supplied as a hard gelatin capsule and indicated to be administered whole with or without food. The efficacy of NEPA was maintained when administered as an oral dose of netupitant given concomitantly (in separate formulations after removal from the hard gelatin capsule) with a single oral dose of palonosetron. At our institution, two patients experienced difficulty swallowing the capsule leading to opening the capsule and individual administration of the medications. We observed that the efficacy was maintained when the opened NEPA capsule was administered as individual medications. We report the details of these two patient cases.

FORMULATION AND EVALUATION OF HARD GELATIN CAPSULES CONTAINING Bacopa Monnieri

Introduction: The present work deals the formulation of hard gelatin capsules containing granules of Brahmi (Bacopa monnieri). Bacopa monnieri is used in Ayurvedic traditional medicine to improve memory and to treat various ailments. The aim of the project is to achieve immediate release of drug from dosage form to achieve therapeutic efficacy and patient compliance. Hard gelatin capsules offer rapid drug release and protection from atmospheric oxygen. Materials and methods: In this work we have prepared the granules of Brahmi and filled into the empty hard gelatin capsule shells. The hard gelatin capsules were then evaluated for dissolution studies, disintegration study, drug content and weight variation. Results and Discussion: After dissolution study it was found that 93.46% of Brahmi was released within 90 min. The kinetics of drug release was also studied and it was found to follow Korsmeyer Peppas model.

Formulation and Evaluation of Liquid Filled Hard Gelatin Capsule of Febuxostat

Liquid filled hard gelatin capsule are well recognized as a solid dosage form for convenient administration of drugs orally in a liquid form. This liquid composition available help the most challenging drug compounds in capsules has increased significantly in recent years. The drugs which have low solubility, poor bioavailability, low melting point, critical stability are the perfect candidate for liquid filling in capsule. The current study presents the formulation aspects, filling and sealing aspects of capsule, evaluation parameters of the liquid filled hard gelatin capsule using Febuxostat as drug, oils (Arachis oil, Coconut oil, Olive oil) as solvents, Glyceryl monostearate as solubilizing agent, Butylated hydroxy toluene as antioxidant, Methyl paraben & Propyl paraben as preservatives. A capsule formed F3 formulation shows maximum drug release and drug content among all the formulations. Keywords: Liquid filled hard gelatin capsule, Febuxostat, Arachis oil, Coconut oil, Olive oil, Glyceryl monostearate, Butylated hydroxy toluene, Methyl paraben, Propyl paraben.

Bioavailability of curcumin from a novel mouth dissolving lozenge

Background: Cucurmin is the main component of curcuminoids in turmeric (Curcuma longa). Turmeric, popularly used as food colourant, is traditionally used as a medicinal herb owing to its antioxidant, anti-inflammatory, antimicrobial and anticancer properties. The gastric absorption of curcumin is poor and therefore various forms like encapsulation in liposomes, polymeric nanoparticles, cyclodextrin encapsulation, lipid complexes, polymer-curcumin complex etc. have been evaluated.Methods: In the current study, a novel lozenge of 100mg turmeric extract in mouth dissolving formulation is evaluated for bioavailability of curcumin as compared with the conventional hard gelatin capsule containing 475mg curcumin. Fourteen healthy male subjects of Indian origin are dosed in a two way, two treatments, two sequence cross-over balanced, randomized design. Blood samples are collected sequentially to cover the plasma concentration-time curve to obtain a reliable estimate of the extent of absorption. Blood plasma is processed and analyzed using a validated isocratic HPLC-MS/MS method to estimate the concentration of curcumin.Results: Curcumin is detected at m/z 369à177, while the internal standard diazepam is detected as m/z 285à193 to quantify curcumin. Results indicate a significant increase in bioavailability of curcumin from the lozenge (Cmax188.863±22.9620ng/ml; AUC0-t 897.026±65.4844ng/mL*hr) as compared to the hard gelatin capsule (Cmax 96.458±15.8272ng/ml; AUC0-t 440.744±77.3470ng/ml*hr).Conclusions: Mouth dissolving lozenge could be a pragmatic approach to circumvent the low bioavailability of curcumin from therapeutic formulations.

Modulation of Drug Release from Natural Rubber Coated Capsule Loaded with Sodium Bicarbonate and Camphor

Natural rubber (NR) has the distinguished film forming and hydrophobic properties. If it could be reformed by an addition of some pore forming agents, the porous topography of this produced material would be interesting for applying in controlled release system. The purpose of this study is to investigate on characterization of film coat and release of propranolol hydrochloride (P) from capsules coated with NR latex. The experimental methods involved the preparation of NR film which was optimally prepared by dipping technique followed by drying onto hard gelatin capsule. The drug release was determined for coated systems fabricated with two different techniques (the dissolving of sodium bicarbonate and the sublimation of ammonium carbonate or camphor). It indicated that ammonium carbonate was incompatible with NR latex. The extent of overall in vitro release of P into HCl buffer pH 1.2 from plain NR film coated capsule at 8 h was approximately 1%. However, the decrease concentration of NR latex or addition of sodium bicarbonate or camphor could enhance the extent of drug release. Scanning electron microscopy (SEM) exhibited the micro porous nature for systems loaded with sodium bicarbonate or camphor. Therefore the hydrophobic nature of NR was proper for sustainable drug release which an incorporation of some poring agent could modulate the release of active compounds.

COMPATIBILITY STUDIES OF ACETAZOLAMIDE WITH EXCIPIENTS BY USING HIGHPERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) TECHNIQUE

Compatibility studies are essential for preformulation studies of formulation development. Acetazolamideis a carbonic anhydrase inhibitor used in the treatment and management of cardiac oedema, glaucomaand other conditions. The objective of this study was to evaluate the physical and chemical stability ofacetazolamide, when mixed with excipients as binary mixture. These samples were stored and evaluatedfor related substances at 400/75 % RH for 28 days and 550 for 14 days and the samples were analyzedusing HPLC. The results demonstrated the suitability of acetazolamide with Avicel PH 101, MethocelK4M premium CR hydroxy propyl methyl cellulose, Methocel E10M premium CR hydroxy propyl methylcellulose, talc, sodium lauryl sulphate and size 00 white/white hard gelatin capsule.