International collaborative study to evaluate and calibrate two recombinant L chain Ferritin preparations for use as a WHO International Standard

Objectives To evaluate and calibrate two candidate preparations for the 4th International Standard for Ferritin (Human, Recombinant) (codes: 19/118 and 19/162) against the 3rd International Standard for Ferritin (Human, Recombinant) (code: 94/572), and three serum commutability samples in an international collaborative study involving 12 laboratories in nine countries. Methods Eleven of the 12 participating laboratories performed Ferritin quantitation using automated assay platforms and one laboratory used a manual ELISA kit. Results There was better overall agreement between all laboratories and between assay methods for the potency of preparation 19/118 than for preparation 19/162. The overall geometric mean potency (from all methods) of the candidate 4th International Standard, 19/118, was 10.5 µg/ampoule, with inter-laboratory variability, expressed as % geometric coefficient of variation (GCV), of 4.7%. Accelerated stability studies have predicted both 19/118 and 19/162 to be very stable for long term storage at −20 °C. Conclusions The candidate 4th International Standard for Ferritin (Human, Recombinant) (19/118) has been shown to be immunologically similar to the 3rd International Standard for Ferritin (Human, Recombinant) (94/572). It was recommended to and accepted by the WHO Expert Committee on Biological Standardization that 19/118 be established as the 4th International Standard for Ferritin (Human, Recombinant) with an assigned potency of 10.5 µg/ampoule and expanded uncertainty limits 10.2–10.8 µg/ampoule (95% confidence; k=2.23).

Formulation and Evaluation of colon targeted drug Delivery of Diloxanide furoate Tablets using pH Dependent Polymers

Diloxanide Furoate is a Dichloroacetamide derivative utilized for the treatment of various protozoal infections like amoebiasis. Colon targeted tablets were designed using pH sensitive polymers like Eudragit S100, Eudragit L 100,Cellulose acetate phthallate at different concentrations. All the matrix,compression coated formulations showed the desired physicochemical properties as per the official limits. The drug release studies were performed according to the USP paddle method by using 0.1N HCL for 2 hours, pH 7.4 phosphate buffer for 3 hours and pH 6.8 phosphate buffer upto 18 hours. A better controlled drug release was shown for Eudragit L 100. Based on the comparative drug release studies among different Formulations F9 with Eudragit L 100 polymer showed better control drug release. The release kinetics for the Optimised Formulation F9 was calculated and “r2” value was more for Zero order kinetics i.e.,0.970 indicating that the formulation doesnot depend upon its concentration and from the Korsmeyer peppas model the diffusion exponent value “n” is > 1 indicating that it follows super case II transport mechanism. The accelerated stability studies conducted for optimised formulation F9 for 3 months have no significant variation.

Physicochemical Evaluation of Diploknema butyracea Seed Extract and Formulation of Ketoconazole Ointment by Using the Fat as a Base

The fat obtained from the ripened seeds of Diploknema butyracea is widely used as a vegetable oil in rural areas of Nepal. This study was aimed for the physicochemical evaluation (acid value, iodine value, saponification value, peroxide value, ester value, pH, and liquefaction point) of the Diploknema butyracea seed extract (chyuri fat) and the formulation of 2% w/w ketoconazole ointment by using it as a base. All the physicochemical parameters were determined quantitatively by using the method of Indian Pharmacopoeia (IP), volume-I. By fusion method, 3 different formulations F-A, F-B, and F-C were prepared, in which different proportions of chyuri fat, polyethylene glycol 6000 (PEG 600), Tween 80, and propylene glycol were used as an ointment base. Various quality parameters such as spreadability, extrudability, viscosity, smoothness, pH, average fill weight, assay, content uniformity, accelerated stability, and drug release profiles were determined. HPLC was used for the determination of ketoconazole content in the ointment formulations. Physicochemical evaluation of the chyuri fat ensured its suitability for industrial purpose. The active ingredient release profile of formulations F-A (87.71%), F-B (88.89%), and F-C (91.09%) after 5 hours were within acceptable range along with other parameters. Assay of the formulations F-A, F-B, and F-C were reported to be 103.01, 107.9, and 102.45%, respectively. Overall, evaluation of the formulation F-A, prepared by using chyrui fat only, gave satisfactory results and most of the parameters were statistically similar ( p > 0.05 ) to the F-B and F-C formulated by incorporating a certain proportion of synthetic base. Thus it can be concluded that chyuri fat can be the best alternative to replace the expensive synthetic base.

Design, Development and Evaluation of Instant Release Oral Thin Films of Flunarizine

The main objective of the present study was to prepare and evaluate the instant release oral thin films of Flunarizine, in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The instant release oral thin films of Flunarizine were prepared by solvent casting method using film forming polymer like Hydroxypropyl Methylcellulose E-15. The film was evaluated for various physicochemical parameters that include thickness, weight variation, folding endurance, tensile strength, drug content and in vitro drug release studies. No differences were observed in in vitro dissolution of drug from the formulated film F1-F9 as the film instantly gets wet by dissolution medium. The drug release for F5 formulations was about 98.1%. The accelerated stability studies for the optimized film formulations F5 were performed that indicates that the formulated instant release oral thin films were unaffected after initial and 3 months storage under accelerated conditions.

Preparation and Evaluation of Topical Microemulsion System Containing Metronidazole

Metronidazole is a synthetic nitroimidazole derived with antimicrobial and anti-inflammatory properties. The aqueous solubility of this drug is poor which results from low bioavailability. Limited effects on the removal of bacteria are shown in the local administration of plain metronidazole. The microemulsion system proves the efficacy of solubility and dissolution improvement of poorly watersoluble drugs such as metronidazole. The objective of this project work is to prepare and evaluate metronidazole containing topical water-in-oil microemulsion and to compare its effectiveness to other commercially available products. In this formulation, tween 80 is used as a surfactant and PEG 400 is used as a co-surfactant. In the oil phase, isopropyl myristate is used. Distilled water is used as the hydrophilic phase. The formulation of metronidazole containing microemulsion was evaluated for physicochemical parameters like pH, viscosity, conductivity, accelerated stability studies. In vitro release study was also performed to evaluate the release kinetics.

Preparation and Evaluation of a Novel Oral Microemulsion Drug Delivery System for Enhancing the Bioavailability of Diltiazem

Diltiazem, a calcium ion cellular influx inhibitor is known for its limited and variable bioavailability. This study is intended to explore the benefits of microemulsion formulation as an oral drug delivery system for immediate release to improve the bioavailability and efficacy of Diltiazem. Methods: Oil in water microemulsion was prepared using the simple water titration method. The optimized formulation was evaluated for physicochemical parameters like viscosity, pH, conductivity, and accelerated stability studies. In vitro release, diltiazem microemulsion was investigated.

Use of Stability Modeling to Support Accelerated Vaccine Development and Supply

Stability assessment of pharmaceuticals in specific storage and shipment conditions is a key requirement to ensure that safe and efficacious products are administered to patients. This is particularly relevant for vaccines, with numerous vaccines strictly requiring cold storage to remain stable. When stability evaluation is exclusively based on real-time data, it may represent a bottleneck for rapid and effective vaccine access. Stability modeling for vaccines represents a key resource to predict stability based on accelerated stability studies; nevertheless, this approach is not fully exploited for these kinds of products. This is likely because of the complexity and diversity of vaccines, as well as the limited availability of dedicated guidelines or illustrative case studies. This article reports a cross-company perspective on stability modeling for vaccines. Several examples, based on the direct experience of the contributors, demonstrate that modeling approaches can be highly valuable to predict vaccines’ shelf life and behavior during shipment or manipulation. It is demonstrated that modeling methodologies need to be tailored to the nature of the vaccine, the available prior knowledge, and the monitored attributes. Considering that the well-established strategies reported in ICH or WHO guidelines are not always broadly applicable to vaccines, this article represents an important source of information for vaccine researchers and manufacturers, setting the grounds for further discussion within the vaccine industry and with regulators.