Biomedical subjects

Linda A Felton

Publications and source records attributed to Linda A Felton.

8 recordsLinked to original sources

PubMed2005

Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen.

Each year millions of people are overexposed to the sun resulting in photodamage of the skin. Secondary photoprotection is the application of medicinal agents to the body after sun exposure to reduce this damage. The objective of this study was to determine the affects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the secondary photoprotective properties of topically applied ibuprofen. Complexation of ibuprofen by HPCD was demonstrated by differential scanning calorimetry, while solubilities were determined using HPLC. A linear (r2>0.999) relationship was found between ibuprofen solubility and HPCD concentration. For subsequent experiments, the concentration of ibuprofen was held constant at the solubility in 10% HPCD (10.6 mg/ml), while the HPCD concentration varied from 0 to 20% (w/w). In vitro transdermal permeation experiments demonstrated a parabolic relationship between transdermal kinetic parameters and HPCD concentration, with maximum values for both flux and skin accumulation occurring with the 10% HPCD formulation. In vivo experiments were performed by exposing hairless mice to UV radiation and applying ibuprofen-HPCD formulations topically at various times following UV exposure. Edema and epidermal lipid damage data demonstrated that application of ibuprofen-HPCD formulations within 1h of UV exposure provided significant photoprotection.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2004

Influence of cyclodextrin complexation on the in vivo photoprotective effects of oxybenzone.

The objective of the current study was to investigate the influence of cyclodextrin complexation on the in vivo photoprotective effects of a model ultraviolet (UV) absorber, oxybenzone, and to compare these novel sunscreens to a commercial SPF 30 sunscreen product. Aqueous-based solutions and suspensions containing 2.7 mg/mL oxybenzone and up to 20% (w/w) hydroxypropyl-beta-cyclodextrin (HPCD) were prepared. The sunscreens were applied to the dorsal skin of SKH-1 hairless mice and the animals were exposed to up to two minimal erythemal doses (MEDs) of UV radiation. Control animals received no sunscreen treatment. Lipid damage, as quantified by decreases in the lipid melting temperature of the epidermis, was determined using differential scanning calorimetry immediately after UV exposure. The number of sunburn cells (SBCs) and the extent of edema were measured 24 hours postexposure. Results showed that all oxybenzone-containing formulations decreased the number of SBCs formed, diminished swelling, and reduced the physical damage to the skin structure, in comparison to control. Thus, complexation did not prevent oxybenzone from reacting with light. The 20% HPCD formulation exhibited more substantial photoprotection at UV exposures of one or two MEDs, as evidenced by the formation of fewer SBCs. The 5% HPCD formulation also provided substantial protection against epidermal lipid damage. These studies demonstrate that inclusion of HPCD in sunscreen formulations may enhance the in vivo photoprotective effects of the UV absorbers. No single HPCD-containing sunscreen, however, was found to be equivalent to a commercially available sunscreen product for all biomarkers investigated.

Animals↗

PubMed2003

Blinding controlled-release tablets for clinical trials.

The objective of the current study was to develop a method to blind commercially available Wellbutrin SR 150 mg sustained-release tablets for a clinical study. Overcoating was selected as the most appropriate blinding method. Hydroxypropyl methylcellulose (Opadry II) containing red iron oxide and titanium dioxide was applied to the Wellbutrin tablets at coating levels ranging from 0.5% to 4% weight gain. When compared against the uncoated product, no significant differences in drug release were noted over an 8-hr period. Matching placebo tablets, prepared using specially designed tablet tooling, were coated with the same cellulosic polymer that was used for the active. The coated active and placebo tablets were virtually indistinguishable. To test the applicability of this overcoating technique for blinding other controlled release products, the same procedure was used to coat Glucotrol XL 5 mg tablets and Theo-Dur 200 mg tablets. The debossing on the Theo-Dur tablets and the laser-drilled hole on the surface of the Glucotrol tablets prevented blinding. The Theo-Dur tablets were mechanically weak and not able to withstand the coating process. Dissolution testing revealed significantly higher amounts of drug were released from the blinded Glucotrol tablets compared to the unblinded product at the 12 hr time point. The findings from this study suggest that overcoating with pigmented hydroxypropyl methylcellulose may not be useful for blinding all controlled-release tablets.

Administration, Oral↗

PubMed2002

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.

Administration, Cutaneous↗

PubMed2002

Influence of insoluble excipients on film coating systems.

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.

Excipients↗

PubMed2002

Weight and weight uniformity of hard gelatin capsules filled with microcrystalline cellulose and silicified microcrystalline cellulose.

The objective of this study was to investigate the weight and weight uniformity of hard gelatin capsules filled with microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC) powdered formulations. A tamping-type encapsulation apparatus was used to fill the capsules. The four formulations that were tested included MCC alone, MCC blended with fumed silica, SMCC, and high-density SMCC (SMCC-HD). The mean capsule weight and the average variation in mean capsule weight of each formulation were determined. Both SMCC products exhibited better flow than the MCC alone, with SMCC-HD being the freest flowing of the powders investigated. Capsules filled with the SMCC products had higher fill weights than those containing the MCC powders. The SMCC-containing capsules exhibited the lowest variation in weight, although these findings were not significantly different from either of the MCC-containing capsules. Significantly higher weight variations were found in capsules filled with SMCC-HD. A relationship between Carr's compressibility index and capsule weight variation was found, with more compressible materials producing more uniformly filled capsules. No relationship could be established between powder flow and capsule weight uniformity. These findings suggest that powder flow may not be a critical parameter in ensuring capsule weight uniformity when the encapsulation equipment utilizes a tamping-type filling system.

Capsules↗

PubMed2002

Influence of hydroxypropyl-beta-cyclodextrin on the transdermal permeation and skin accumulation of oxybenzone.

The objective of the present study was to determine the effects of hydroxypropyl-beta-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.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2002

A novel technique to quantify film--tablet interfacial thickness.

The purpose of the project was to develop an x-ray photoelectron spectroscopic technique to quantify film-tablet interfacial thickness. Tablets containing 99% dibasic calcium phosphate were coated with an acrylic polymer containing chlorine (Eudragit RL 30 D). The film-tablet interface was defined as the region where phosphorous from the tablet and chlorine from the film coating were detected simultaneously. Five-minute intermittent ion-sputtering was used in conjunction with the conventional x-ray photoelectron spectroscopy to achieve depth profiling of the sample. The slow ion-sputtering rate of approximately 56 nm/min was overcome through sample preparation and analysis from the tablet side of the sample. This process eliminated the need to sputter through the entire film coating to reach the area of interest. Initially, only phosphorous from the tablet was detected. As the depth profiling proceeded, the chlorine signal increased and the relative intensity of the phosphorous decreased. By plotting the relative intensities of each element against the ion-sputtering time and using linear regression, the point at which the two lines intersected (tmid) was determined. By doubling tmid and multiplying by the estimated ion-sputtering rate, the thickness of the film-tablet interface was estimated to be approximately 34 microns. Further studies are needed to correlate the film-tablet interfacial thickness with the adhesive properties of coated solids.

Tablets↗