Linda A. Felton

Influence of Transcutol CG on the skin accumulation and transdermal permeation of ultraviolet absorbers.

The objective of this study was to determine the influence of Transcutol CG concentration on the transdermal permeation and skin accumulation of two ultraviolet (UV) absorbers, 2-hydroxy-4-methoxybenzophenone (oxybenzone) and 2-octyl-4-methoxycinnamate (cinnamate). The concentration of the UV absorber was held constant at 6% (w/w) for all vehicle systems while the concentration of Transcutol CG was varied from 0 to 50% (w/w). Data showed that both UV absorbers exhibited increases in skin accumulation with increasing concentrations of Transcutol CG. Skin accumulation of oxybenzone was significantly (P<0.05) greater than that of cinnamate for all formulations investigated. Oxybenzone skin accumulation ranged from 22.9+/-2.8 microg/mg (0% Transcutol CG) to 80.8+/-27.2 microg/mg (50% Transcutol CG). Cinnamate skin accumulation ranged from 9.0+/-0.9 microg/mg to 39.8+/-12.2 microg/mg at 0 and 50% Transcutol CG, respectively. No significant differences were found in the transdermal permeation of oxybenzone or cinnamate for any of the formulations tested. The results of this study demonstrate that the inclusion of Transcutol CG in sunscreen formulations increases the skin accumulation of the UV absorbers oxybenzone and cinnamate without a concomitant increase in transdermal permeation.

Physical and enteric properties of soft gelatin capsules coated with eudragit ® L 30 D-55

Abstract The enteric coating of soft gelatin capsules (SGC) containing ibuprofen in either PEG 400 or Miglyol© was investigated. The effects of two plasticizers, triethyl citrate (TEC) and tributyl citrate (TBC), on the physical and enteric properties of SGC coated with Eudragit ® L 30 D-55 were studied. The water soluble plasticizer TEC was found to be a good plasticizing agent for the Eudragit® L 30 D-55 irrespective of the fill liquid, while the TBC provided satisfactory results only for capsules containing the hydrophobic fill liquid, Miglyol ®. The combination of TEC and TBC provided effective plasticization for the acrylic coating regardless of the fill liquid. A subcoat of HPMC showed no effect on the enteric protection of either Miglyol® - and PEG-containing capsules that were stored at room temperature and zero percent relative humidity. The moisture content of the gelatin shell of the film coated SGC stored at room temperature and at 0 or 96% relative humidity was followed as a function of time. The load strength of the capsules was measured during 3 months of storage using an Instron universal testing apparatus, and the physical-mechanical properties of the capsules were correlated with the moisture content of the SGC. As the moisture content of the gelatin decreased, all formulations exhibited an increase in load strength.

Influence of plasticizers on the adhesive properties of an acrylic resin copolymer to hydrophilic and hydrophobic tablet compacts

The influence of plasticizers in film coating formulations on the adhesive properties of an acrylic resin copolymer was determined using the butt adhesion technique. Hydrophilic and hydrophobic plasticizing agents were incorporated into aqueous dispersions of Eudragit® L 30 D-55 and coated onto hydrophilic and hydrophobic tablet compacts. Using data obtained from a Chatillon digital force gauge attached to a motorized test stand, force-deflection profiles, similar to stress-strain curves generated in the tensile testing of free films, were constructed and the force of adhesion, elongation at adhesive failure, and adhesive toughness were determined. Plasticizer concentration and plasticizer type were found to influence the adhesive properties of the acrylic polymer. An increase in adhesive toughness was found when the concentration of triethyl citrate (TEC) in the coating formulation was increased from 20 to 30%, which was attributed to an increase in the elasticity of the film and a decrease in the internal stresses within the polymer. Films containing water soluble plasticizers were found to adhere more strongly to the tablet compacts than the water insoluble agents, due to more effective disruption of the intermolecular attractions between the polymer chains. Adhesion of the polymer to tablet compacts was found to be significantly influenced by the hydrophobicity of the tablet surface when the water soluble plasticizers were incorporated into the film coating, whereas no significant differences in the adhesive properties were found when the polymer was plasticized with water insoluble agents. Aging of the film-coated tablets resulted in a decrease in adhesive toughness, irrespective of the environmental storage condition.

Adhesion of polymeric films to pharmaceutical solids

The two major forces influencing polymer adhesion include the strength of the interfacial bonds between the polymeric film and the surface of the solid and the internal stresses within the film coating. While good adhesion between the polymer and the substrate is desirable for pharmaceutical products, the small size of the dosage form and the non-uniform surface roughness have created difficulties in assessing polymer adhesion. In this review, the experimental devices and procedures used to quantitate polymer adhesion are addressed. The affects of the physical and chemical properties of the substrate, including surface roughness and tablet hydrophobicity, on adhesion of a polymer to either tablets or capsules are discussed. The influence of the plasticizers, pigments, and solvents in film coating formulations on polymer adhesion, and the effects of aging of the coated solids on adhesion of polymers to tablets and capsules are also discussed.

Influence of Insoluble Excipients on Film Coating Systems

ABSTRACT Insoluble excipients are added to polymeric film coating solutions and dispersions to improve the physical appearance of dosage forms, enhance the stability of photolytic drugs, and aid in processing. These insoluble additives, however, may significantly affect the physical, mechanical, adhesive, and drug-release properties of the films. In this review, the theories of the interactions between polymer and insoluble excipient are addressed. This article also discusses the influence of the concentration, particle size, morphology, and surface chemistry of insoluble excipients on the various polymer properties.

Characterization of coating systems.

Polymeric film coatings have been applied to solid substrates for decorative, protective, and functional purposes. Irrespective of the reasons for coating, certain properties of the polymer films may be determined as a method to evaluate coating formulations, substrate variables, and processing conditions. This article describes experimental techniques to assess various properties of both free and applied films, including water vapor and oxygen permeability, as well as thermal, mechanical, and adhesive characteristics. Methods to investigate interfacial interactions are also presented.

Mechanisms of polymeric film formation.

Polymeric films are applied to solid dosage forms for decorative, protective, and functional purposes. These films are generally applied by a spray atomization process, where the polymer is sprayed onto the solid substrate. The mechanism by which films are formed is dependent on whether the polymer is in the dissolved or dispersed state. For solutions, film formation occurs as the solvent evaporates, since the polymer chains are intimately mixed. Film formation from polymeric dispersions, however, requires the coalescence of individual polymer spheres and interpenetration of the polymer chains. Films prepared from polymeric dispersions exhibit a minimum film forming temperature and processing conditions must exceed this temperature in order to form the film. In addition, these systems generally require post-coating storage in temperature and humidity controlled environments to ensure complete polymer coalescence. Incomplete coalescence can lead to significant changes in drug release over time. This review article highlights the basic science principles involved in film formation from both polymeric solutions and dispersions and the variables that influence these film formation processes.

Influence of hydroxypropyl-β-cyclodextrin on transdermal penetration and photostability of avobenzone

The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the transdermal penetration and photostability of a model ultraviolet A (UVA) absorber, butyl methoxydibenzoylmethane (avobenzone), and to determine the influence of complexation on in vivo photoprotection. Avobenzone-HPCD complexation was demonstrated by differential scanning calorimetry. Formulations containing 0.12 mg/ml avobenzone and up to 30% (w/w) HPCD were prepared. Transdermal penetration was conducted using a modified Franz diffusion cell apparatus. As the concentration of HPCD was increased from 0% to 20%, transdermal permeation increased. Maximum flux occurred at 20% HPCD, where sufficient cyclodextrin was present to completely solubilize all avobenzone. When the concentration of HPCD was increased to 30%, transdermal penetration decreased, suggesting the formation of an avobenzone reservoir on the skin surface. Photostability of avobenzone was investigated under 100, 250, and 500 kJ/m2 UVA irradiation. The 30% HPCD formulation was the most photostable, followed by 20%, 10%, and 0% formulations. In vivo, the 30% HPCD formulation afforded the best photoprotection, as evidenced by the lowest extent of sunburn cell formation and edema induction. This work indicates that inclusion of HPCD in sunscreen formulations may enhance photoprotection by reducing both skin penetration and photodecomposition of UV absorbers.

Influence of Hydroxypropyl- β-Cyclodextrin on the Transdermal Permeation and Skin Accumulation of Oxybenzone

ABSTRACT The objective of the present study was to determine the effects of hydroxypropyl-β-cyclodextrin (HPCD) concentration on the transdermal permeation and skin accumulation of a model ultraviolet (UV) absorber, oxybenzone. The concentration of oxybenzone was held constant at 2.67 mg/mL for all formulations, while the HPCD concentrations varied from 0 to 20% (w/w). Complexation of oxybenzone by HPCD was demonstrated by differential scanning calorimetry. A modified Franz cell apparatus was used in the transdermal experiments, with aliquots of the receptor fluid assayed for oxybenzone by high-performance liquid chromatography. From the permeation data, flux of the drug was calculated. Skins were removed from the diffusion cells at specified time points over a 24-hr period and the oxybenzone content in the skin determined. The aqueous solubility of oxybenzone increased linearly with increasing HPCD concentration, following a Higuchi AL-type complexation. The stability constant of the reaction was calculated from the phase-solubility diagram and found to be 2047 M−1. As the concentration of HPCD was increased from 0 to 10%, transdermal permeation and skin accumulation of oxybenzone increased. Maximum flux occurred at 10% HPCD, where sufficient cyclodextrin was added to completely solubilize all oxybenzone. When the concentration of HPCD was increased to 20%, both transdermal permeation and skin accumulation decreased. These data suggest the formation of a drug reservoir on the surface of the skin.

Physical-mechanical properties of film-coated soft gelatin capsules

Abstract Soft gelatin capsules containing ibuprofen dissolved in either PEG 400 or Miglyol® 812 were coated with an aqueous dispersion of Eudragit® L 30 D-55 using a Mini Hi-Coater. The physical-mechanical properties of the coated capsules, including tensile strength, Youngs modulus and tensile toughness, were determined using a Chatillon DFGS50 force gauge attached to a Chatillon TCD-200 motorized test stand. The diametral compression tests were conducted at a rate of 12.7 mm/minute. Force-deflection curves were obtained and mathematically manipulated to yield stress-strain diagrams. The influence of two plasticizing agents, triethyl citrate (TEC) and tributyl citrate (TBC), on the physical-mechanical properties was determined. The hydrophilic plasticizer TEC was found to be the best plasticizer for the acrylic films, regardless of the fill liquid. The physical-mechanical properties of the coated and uncoated soft gelatin capsules were a function of the fill liquid. Temperature and humidity were found to influence the physical-mechanical properties of the coated capsules. The adhesion between the gelatin capsule and the acrylic polymer was found to be dependent on both the fill liquid and plasticizer in the coating formulation. Coating dispersions plasticized with TEC exhibited good adhesion with both the PEG 400 and the Miglyol® 812, whereas the TBC plasticized film coating showed good adhesion with the Miglyol® 812 fill liquid. The acrylic film coatings for the PEG-containing capsules and plasticized with TBC exhibited an increased adhesion of the polymer to substrate over time when stored at both high temperature and high humidity.