An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms.

Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit(®) L30 D-55, Eudragit(®) EPO, Opadry(®) AMB and Sepifilm(®) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapor sorption at 0 and 75% RH (25°C). Accelerated stability studies were undertaken at 75% RH/25°C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit(®) L30 D-55), 0.35% (Opadry(®) AMB), 0.49% (Sepifilm(®) LP) and 0.76% (Eudragit(®) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit® L30 D-55 coated cores 78.8%; Opadry(®) AMB coated cores 76.2%, Sepifilm(®) LP coated cores 76.0% and Eudragit(®) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms.

A facile approach to manufacturing non-ionic surfactant nanodipsersions using proniosome technology and high-pressure homogenization.

In this study, a niosome nanodispersion was manufactured using high-pressure homogenization following the hydration of proniosomes. Using beclometasone dipropionate (BDP) as a model drug, the characteristics of the homogenized niosomes were compared with vesicles prepared via the conventional approach of probe-sonication. Particle size, zeta potential, and the drug entrapment efficiency were similar for both size reduction mechanisms. However, high-pressure homogenization was much more efficient than sonication in terms of homogenization output rate, avoidance of sample contamination, offering a greater potential for a large-scale manufacturing of noisome nanodispersions. For example, high-pressure homogenization was capable of producing small size niosomes (209 nm) using a short single-step of size reduction (6 min) as compared with the time-consuming process of sonication (237 nm in >18 min) and the BDP entrapment efficiency was 29.65% ± 4.04 and 36.4% ± 2.8. In addition, for homogenization, the output rate of the high-pressure homogenization was 10 ml/min compared with 0.83 ml/min using the sonication protocol. In conclusion, a facile, applicable, and highly efficient approach for preparing niosome nanodispersions has been established using proniosome technology and high-pressure homogenization.

Air-jet and vibrating-mesh nebulization of niosomes generated using a particulate-based proniosome technology.

The aerosol properties of niosomes were studied using Aeroneb Pro and Omron MicroAir vibrating-mesh nebulizers and Pari LC Sprint air-jet nebulizer. Proniosomes were prepared by coating sucrose particles with Span 60 (sorbitan monostearate), cholesterol and beclometasone dipropionate (BDP) (1:1:0.1). Nano-sized niosomes were produced by manual shaking of the proniosomes in deionized water followed by sonication (median size 236nm). The entrapment of BDP in proniosome-derived niosomes was higher than that in conventional thin film-made niosomes, being 36.4% and 27.5% respectively. All nebulizers generated aerosols with very high drug output, which was 83.6% using the Aeroneb Pro, 85.5% using the Pari and 72.4% using the Omron. The median droplet size was 3.32µm, 3.06µm and 4.86µm for the Aeroneb Pro, Pari and Omron nebulizers respectively and the "fine particle fraction" (FPF) of BDP was respectively 68.7%, 76.2% and 42.1%. The predicted extrathoracic deposition, based on size distribution of nebulized droplets was negligible for all devices, suggesting all of them are potentially suitable for pulmonary delivery of niosomes. The predicted drug deposition in the alveolar region was low using the Omron (3.2%), but greater using the Aeroneb Pro (17.4%) and the Pari (20.5%). Overall, noisome-BDP aerosols with high drug output and FPF can be generated from proniosomes and delivered using vibrating-mesh or air-jet nebulizers.

Moisture sorption and permeability characteristics of polymer films: implications for their use as barrier coatings for solid dosage forms containing hydrolyzable drug substances.

Moisture sorption and permeability characteristics of polymer films were studied and their effectiveness to protect a hydrolyzable drug assessed. Cast films were prepared from Eudragit L30 D-55, Eudragit EPO, Opadry AMB and Sepifilm LP dispersions, which were also applied onto tablet cores formulated with aspirin as a model moisture sensitive active ingredient. Sorption studies were undertaken using dynamic vapour sorption, ranging between 0% and 90% RH at 25 degrees C. Cast films exhibited fast equilibration (

The hygroscopicity of moisture barrier film coatings.

The hygroscopicity of three commercial moisture-barrier film coatings, namely, Eudragit L30 D-55 (methacrylic acid-ethyl acrylate copolymer), Opadry AMB (polyvinyl alcohol based system), and Sepifilm LP 014 (hypromellose, microcrystalline cellulose, and stearic acid based formulation), was investigated using a dynamic vapor sorption apparatus. Moisture uptake by cast films and uncoated and coated tablet cores, which were designed to be hygroscopic, low hygroscopic, and waxy, was measured following exposure to repeat relative humidity (RH) cycles of 0-50-0-50-0%, 0-75-0-75-0%, and 0-90-0-90-0% RH at 25 degrees C. Eudragit cast film exhibited the fastest equilibration but was also the least hygroscopic. Sepifilm had the fastest sorption and took up the greatest mass of water. The rate of uptake for Opadry film was similar to Sepifilm. However, this film continued to sorb moisture for a longer period. When returned to 0% RH it retained moisture in the film showing that it had a high affinity for moisture within the film. The data for the different cores indicated that there was very little benefit in using a moisture barrier film on cores with low hygroscopicity, the mass gain being a sum of that which would be expected to sorb to the film and that which sorbs to the uncoated core. There was, however, some advantage for hygroscopic cores where, even though the barrier coatings allowed substantial water sorption into the core, the extent of this was less and the rate of uptake lower than for the uncoated sample.