Evaluation of polyvinyl acetate phthalate as an enteric coating material

A general procedure for the evaluation of enteric coating excipients using the accepted polymeric characterization techniques of membrane osmometry, scanning electron microscopy, solubility determination and titration is described. As a model compound, the excipient functions of the enteric polyelectrolyte polyvinyl acetate phthalate (I), obtained from two sources, designated as polymer A and B, are evaluated and compared. Molecular weights determined by membrane osmometry were 61,000 and 48,000 for polymer A and B, respectively. Scanning electron photomicrographs reveal significant morphological differences between the two materials. The solubilities of A and B are different in various solvents, but their mutual solubilities in solvent coating systems were estimated from a ternary plot of their solubilities versus solvent fractional solubility parameters. The apparent pK_aS of I obtained by titration are not the same for A and B, but are a function of their degree of ionization and decrease as the ionic strength of the titration solution is increased. The molar solubilities of A and B calculated from titration data at 37°C and an average ionic strength of approximately 0.06 M during the titration were 4.45 × 10^?5 M and 6.48 × 10^?5 M, respectively. The neutralization rates of A and B measured by a pH-stat method are equivalent and increased with increasing ionic strength. It was concluded that A and B were functional equivalents and that the characterization methods used in this study are acceptable for use as a general procedure for the evaluation of an enteric coating excipient.     

An approach to a cold chain free oral cholera vaccine: in vitro and in vivo characterization of Vibrio cholerae gastro-resistant microparticles

The present work describes the formulation of Eudragit^® L30 D-55 microparticles (MP) alone or with mucoadhesive agents, alginate or Carbopol^®, as an approach for the development of an oral cholera vaccine. In the first part, a spray drying technique was optimized for microparticle elaboration, obtaining a microparticle size ranging from 7 to 9 μm with high encapsulation efficiencies. Moreover, gastro resistant properties and Vibrio cholerae (VC) antigenicity were maintained, but for Eudragit^®-Carbopol^® microparticles which showed low antigenicity values, ≈25%. Next, a stability study was performed following ICH Q1 A (R2) guidelines, i.e. 25 °C-60% relative humidity (RH) for 12 months, and 30 °C-65% RH and 40 °C-75% RH for 6 months. Upon storage, microparticle size changed slightly, 1 μm for Eudragit^®-alginate MPs and 0.36 μm for Eudragit^®MP. However, gastro resistance and antigenicity values were kept in an acceptance range. In the third stage of this work, in vivo experiments were performed. The immune response evoked was measured by means of vibriocidal titer quantification, observing that Eudragit^®-alginate MPs were able to induce stronger immune responses, comparable to the free VC. Therefore, microencapsulation of VC by spray drying could be proposed as an approach to a cold chain free and effective oral cholera vaccine.     

Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation

Objectives The aim of this study was to determine if spray‐drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation. Methods Trypsin was spray‐dried with raffinose from a methanol : n‐butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co‐spray‐dried with raffinose, trehalose or hydroxpropyl‐β‐cyclodextrin. The spray‐dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in‐vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed. Key findings The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray‐drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl‐β‐cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high‐humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs. Conclusions NPMPs of trypsin : excipient systems can be produced by spray‐drying by adjustment of the solvent system to allow for adequate solubility of trypsin.