The effect of dilution of fusidic acid cream and betamethasone dipropionate cream in complex extemporaneous mixes on formulation performance.

The Aron regimen is an unconventional therapy which entails frequent applications of an extemporaneously prepared three component system (a topical antibiotic, a corticosteroid and an emollient), with the intention of decolonising the skin of S. aureus whilst treating atopic dermatitis. The impact of heavily diluting these topical medicinal products, to differing extents, on formulation performance is not well understood thus was investigated in this study. Following a single application of a range of compounded Aron mixes (fusidic acid and betamethasone dipropionate diluted to varying extents in an emollient base), significant reductions in the expected drug flux across silicone membrane, ex vivo percutaneous absorption and skin retention of both drugs relative to the marketed products were observed. This was attributed to a number of complex formulation effects making such changes difficult to predict in a clinical setting. Further investigations are required to evaluate the impact of frequent applications of the Aron mix to widespread areas on clinical efficacy, antimicrobial resistance and long term side effects.

The use of optical differential scanning calorimetry to investigate ibuprofen miscibility in polymeric films for topical drug delivery.

Understanding drug miscibility in pharmaceutically relevant systems is essential for the development and optimisation of pharmaceutical dosage forms. This is particularly true for film forming systems which are designed to become supersaturated with drug, following application on the skin surface, whilst maintaining the physical stability of the drug for a suitable period to enhance drug delivery. For such formulations, chemical penetration enhancers as well as the drug are absorbed from the formulation into the skin, making understanding drug delivery from the films challenging. This study investigated the use of an optical differential scanning calorimetry (DSC) to understand drug miscibility in polymeric film forming systems and explain drug transport behaviour from film forming formulations, containing ibuprofen, a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate (Eudragit® E, EuE), a copolymer based on ethyl acrylate, methyl methacrylate and methacrylic acid ester with quaternary ammonium groups (Eudragit® RS, EuRS) and a copolymer based on methacrylic acid and methyl methacrylate (Eudragit® S, EuS), with and without the chemical penetration enhancer propylene glycol, across a model membrane. The optical DSC enabled the rapid screening of not only drug-polymer miscibility, but also drug-vehicle miscibility, while considering both the melting-point depression and melting enthalpy of the drug due to the presence of the polymer/polymer-based vehicle, obtained via thermal analysis by structural characterisation (TASC) and DSC analysis, respectively. The results obtained enable the polymers studied to be ranked in the order of EuE > EuRS > EuS, with EuE being more miscible with ibuprofen, and the incorporation of a penetration enhancer in the film forming system formulation was found to increase ibuprofen solubility in EuE- and EuRS- based films. The drug-polymer/vehicle miscibility information obtained via optical DSC provided understanding of drug transport from film forming systems with the higher miscibility of ibuprofen with EuE reducing drug transport through decreasing drug saturation in the film. The higher drug transport from films containing EuRS and EuS could also be linked to drug miscibility with the polymer and showed dependence on ibuprofen loading in the formulation. Overall optical DSC has been demonstrated to be a valuable tool for determining drug-vehicle miscibility for pharmaceutical product development.

Correction to: Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers.

The article Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers, written by Farah, Brown, and McAuley was originally published electronically on the publisher's internet portal on 31 May, 2020 without open access.

Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers.

PURPOSE: The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations of heat and use of specific chemical penetration enhancers. METHODS: Franz cell experiments with human scalp skin were performed with a range of chemical penetration enhancers at 32°C and 45°C to simulate normal and heated conditions. Selected chemical penetration enhancers were taken forward for finite dose Franz cell studies which examined the effect of heat produced by a prototype external heating system that supplied either 20 or 30 min of additional heat over both a 24 h and a 1 h time period. RESULTS: Short durations of externally applied heat significantly increased finasteride penetration into human scalp skin after 24 h. Analysis of drug distribution in the skin after 1 h and 24 h indicated that both heat and chemical penetration enhancer selection influenced drug delivery to the hair follicles. CONCLUSION: The use of short durations of heat in combination with specific chemical penetration enhancers was able to increase the delivery of finasteride to human scalp skin and provide focussed drug delivery to the hair follicles.

The use of heat and chemical penetration enhancers to increase the follicular delivery of erythromycin to the skin.

The effect of heat on the follicular absorption of drugs into the skin has not previously been investigated. In comparison to drug delivery across the continuous stratum corneum (SC), follicular absorption is known to be relatively rapid and therefore the use of short durations of heat may be particularly useful for enhancing drug delivery to the hair follicles, as well as being practical for patients to use. In this study erythromycin has been used as a model drug and the combined use of heat and chemical penetration enhancers was found to be able to synergistically increase the penetration of erythromycin into human skin via the follicular route. Moreover durations of heat application as short as 10 min in combination with particular enhancer systems were found to be sufficient to significantly increase erythromycin delivery to the skin. Overall the data indicate that the use of heat with chemical penetration enhancers offers a potentially valuable strategy for delivering drugs via the follicular route.

Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate.

Film forming systems offer a number of advantages for topical and transdermal drug delivery, in particular enabling production of a supersaturated state which can greatly improve drug absorption and bioavailability. However the suitability of individual film forming polymers to stabilise the supersaturated state and optimise delivery of drugs is not well understood. This study reports the use of differential scanning calorimetry (DSC) to measure the solubility of methylphenidate both as the free base and as the hydrochloride salt in two polymethacrylate copolymers, Eudragit RS (EuRS) and Eudragit E (EuE) and relates this to the ability of films formed using these polymers to deliver methylphenidate across a model membrane. EuRS provided greater methylphenidate delivery when the drug was formulated as the free base in comparison EuE because the lower solubility of the drug in EuRS provided a higher degree of drug saturation in the polymeric film. In contrast EuE provided greater delivery of methylphenidate hydrochloride as EuRS could not prevent its crystallisation from a supersaturated state. Methylphenidate flux across the membrane could be directly related to degree of saturation of the drug in the film formulation as estimated by the drug solubility in the individual polymers demonstrating the importance of drug solubility in the polymer included in film forming systems for topical/transdermal drug delivery. In addition DSC has been demonstrated to be a useful tool for determining the solubility of drugs in polymers used in film forming systems and the approaches outlined here are likely to be useful for predicting the suitability of polymers for particular drugs in film forming transdermal drug delivery systems.

An investigation of how fungal infection influences drug penetration through onychomycosis patient's nail plates.

The treatment of onychomycosis remains problematic even though there are several potent antifungal agents available for patient use. The aim of this investigation was to understand whether the structural modifications that arise when a patient's nail become infected plates influences the permeation of drugs into the nail following topical application. It was hoped that through improving understanding of the nail barrier in the diseased state, the development of more effective topical treatments for onychomycosis could be facilitated. The permeation of three compounds with differing hydrophobicities, caffeine, terbinafine and amorolfine (clogD at pH 7.4 of -0.55, 3.72 and 4.49 respectively), was assessed across both healthy and onychomycosis infected, full thickness, human nail plate sections. Transonychial water loss (TOWL) measurements performed on the healthy and diseased nails supported previous observations that the nail behaves like a porous barrier given the lack of correlation between TOWL values with the thicker, diseased nails. The flux of the more hydrophilic caffeine was twofold greater across diseased in comparison with the healthy nails, whilst the hydrophobic molecules terbinafine and amorolfine showed no statistically significant change in their nail penetration rates. Caffeine flux across the nail was found to correlate with the TOWL measurements, though no correlation existed for the more hydrophobic drugs. These data supported the notion that the nail pores, opened up by the infection, facilitated the passage of hydrophilic molecules, whilst the keratin binding of hydrophobic molecules meant that their transport through the nail plate was unchanged. Therefore, in order to exploit the structural changes induced by nail fungal infection it would be beneficial to develop a small molecular weight, hydrophilic antifungal agent, which exhibits low levels of keratin binding.

Human nail plate modifications induced by onychomycosis: implications for topical therapy.

PURPOSE: Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. METHODS: The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail's density was determined via pycnometry and the nail's ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake. RESULTS: Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm(3); diseased 1.29 ± 0.00 g/cm(3)). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle. CONCLUSIONS: Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.

The effects of esterified solvents on the diffusion of a model compound across human skin: an ATR-FTIR spectroscopic study.

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to investigate the effects of three fatty acid esters on skin permeation. Propylene glycol diperlargonate (DPPG), isopropyl myristate (IPM) and isostearyl isostearate (ISIS) were selected as pharmaceutically relevant solvents with a range of lipophilicities and cyanophenol (CNP) was used as a model drug. The resultant data were compared with that obtained when water was used as the solvent. The diffusion of CNP, DPPG and IPM across epidermis was successfully described by a Fickian model. When ISIS was used as a solvent Fickian behaviour was only obtained across isolated stratum corneum suggesting that the hydrophilic layers of the epidermis interfere with the permeation of the hydrophobic ISIS. The diffusion coefficients of CNP across epidermis in the different solvents were not significantly different. Using chemometric data analysis diffusion profiles for the solvents were deconvoluted from that of the skin and modelled. Each of these solvents was found to diffuse at a faster rate across the skin than CNP. DPPG considerably increased the concentration of CNP in the stratum corneum in comparison with the other solvents indicating strong penetration enhancer potential. In contrast IPM produced a similar CNP concentration in the stratum corneum to water with ISIS resulting in a lower CNP concentration suggesting negligible enhancement and penetration retardation effects for these two solvents respectively.

The effect of medical nutrition therapy on changes in dietary knowledge and DASH diet adherence in older adults with cardiovascular disease.

OBJECTIVE: To examine the effect of MNT on dietary knowledge of older adults at baseline, 6 months and 12 months and to assess the effect of dietary knowledge on change in DASH diet adherence from baseline to 12 months. DESIGN: Data for the analysis come from a controlled, randomized prospective design conducted from 2003-2005 with the outcome measures taken pre-, mid-, and post-intervention. SETTING: Data were collected from participants in their homes in an urban community in North Carolina. PARTICIPANTS: Participants (N=147) were adults aged 60+ with a diagnosis of hypertension and/or hyperlipidemia. INTERVENTION: Intervention recipients received three sessions of MNT throughout the 1 year study period. The control group received nutrition information at enrollment. MEASUREMENTS: Participants completed a dietary knowledge questionnaire and a 24 dietary recall at baseline, 6 months, and 12 months. Instrumental variables models with participant fixed effects were used to determine the impact of MNT on dietary knowledge and dietary knowledge on DASH diet adherence. RESULTS: Among those who received MNT, dietary knowledge increased from baseline to twelve months (p<.01). Changes in dietary knowledge were not associated with changes in DASH adherence from baseline to 12 months (p=0.44). CONCLUSIONS: The MNT administered was effective at improving dietary knowledge, but not at improving DASH adherence. Three MNT sessions may be insufficient to change behavior. Integrating behavioral change theory and cultural sensitivity to MNT may improve diet adherence among diverse older adults.

Opto-Thermal Transient Emission Radiometry (OTTER) to image diffusion in nails in vivo.

This work describes the first application of Opto-Thermal Transient Emission Radiometry (OTTER), an infrared remote sensing technique, to probe the extent to which solvents permeate the human nail in vivo. Decanol, glycerol and butyl acetate were selected as model solvents. After application of the solvents, individually, to human volunteers, OTTER was used to depth profile the solvents. The permeation rate of the solvents was ranked as glycerol>decanol>butyl acetate. It is possible that some of the butyl acetate may have evaporated during the experiment. The ability of decanol to extract lipids from biological tissue is also considered. These preliminary results demonstrate the potential of OTTER as a tool to identify optimal excipients with which to target drugs to the nail.

Thermodynamic considerations of solvent/enhancer uptake into a model membrane.

The aim of this study was to conduct a thermodynamic analysis of the uptake of solvents into a model membrane as a precursor to skin transport studies. The investigation was designed so that the methodology may be applied to analyse data produced from measurement of the uptake of enhancers into skin. The uptake of a series of alcohols into polydimethylsiloxane (silicone) membranes in the temperature range 5-45 degrees C was examined. A thermodynamic analysis of the data was performed to provide fundamental insight into the uptake process. A simple structure activity relationship was found to exist for the uptake of alcohols with a carbon chain length greater than four, with additional methylene groups exponentially decreasing the equilibrium uptake. Two separate straight lines were observed in the van't Hoff plot for the equilibrium solvent uptake above and below 16 degrees C. The two separate straight lines in the van't Hoff plot suggest a change in the mechanism of solvent uptake and solvent structure in the membrane above and below 16 degrees C. This is likely to have implications for the effect of the solvents on the partitioning of drugs into the membrane and will be used to provide insight into dynamic measurements of the effect of temperature on the transport of drug molecules in the same vehicles, across the membrane. The analysis described here should provide a useful methodology for investigating the uptake of solvents into model membranes.

ATR-FTIR spectroscopy and spectroscopic imaging of solvent and permeant diffusion across model membranes.

The uptake and diffusion of solvents across polymer membranes is important in controlled drug delivery, effects on drug uptake into, for example, infusion bags and containers, as well as transport across protective clothing. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy has been used to monitor the effects of different solvents on the diffusion of a model compound, 4-cyanophenol (CNP) across silicone membrane and on the equilibrium concentration of CNP obtained in the membrane following diffusion. ATR-FTIR spectroscopic imaging of membrane diffusion was used to gain an understanding of when the boundary conditions applied to Fick's second law, used to model the diffusion of permeants across the silicone membrane do not hold. The imaging experiments indicated that when the solvent was not taken up appreciably into the membrane, the presence of discrete solvent pools between the ATR crystal and the silicone membrane can affect the diffusion profile of the permeant. This effect is more significant if the permeant has a high solubility in the solvent. In contrast, solvents that are taken up into the membrane to a greater extent, or those where the solubility of the permeant in the vehicle is relatively low, were found to show a good fit to the diffusion model. As such these systems allow the ATR-FTIR spectroscopic approach to give mechanistic insight into how the particular solvents enhance permeation. The solubility of CNP in the solvent and the uptake of the solvent into the membrane were found to be important influences on the equilibrium concentration of the permeant obtained in the membrane following diffusion. In general, solvents which were taken up to a significant extent into the membrane and which caused the membrane to swell increased the diffusion coefficient of the permeant in the membrane though other factors such as solvent viscosity may also be important.

Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis.

In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

Preparing future aging advocates: the Oklahoma Aging Advocacy Leadership Academy.

PURPOSE: This article describes the organization, operation, and evaluation of the Oklahoma Aging Advocacy Leadership Academy (OAALA). DESIGN AND METHODS: The Academy was designed to assure the continuation of future cohorts of advocates and volunteers for aging programs and services. It is a statewide training program consisting of 10 weekend sessions. The curriculum incorporates age-related content and advocacy/leadership/voluntary skills training. Evaluation consisted of: (a) a pre-post assessment of perceived familiarity with advocacy and volunteer leadership issues; (b) post-Academy participant assessments of the quality of various aspects of the Academy; (c) post-Academy written statements about areas that were valuable and in need of change; and (d) a compilation of student volunteer and advocacy activities. RESULTS: Evaluation results indicate that the OAALA led to significant increases in perceived familiarity with issues and very positive participant assessments of quality. In addition, many participants spontaneously initiated advocacy and volunteer activities while enrolled in the Academy. IMPLICATIONS: Our experience with the Academy suggests that it is a feasible means of preparing individuals to become successful old-age advocates and volunteer leaders.

Private pay clients in adult day services.

Data collected for all 3,992 participants in Maryland's adult day care programs as of December 31, 1993 showed that the majority of clients were supported by publicly supported "welfare" funding sources. The authors examined the differences in characteristics and service needs between the public payer population and private pay patients, including those who were charged on a sliding scale. They found that private pay clients were not dependent on others to "initiate service arrangements when they want and can find them." Private pay clients were twice as likely to be self or family referrals and more likely to be older, white, and living with a spouse or adult child. Private pay patients were also much more likely to have a history of the recent onset of cognitive impairment and associated memory loss but less likely to fall into the more ADL dependent categories. The nuclear families of private pay clients who are primary caregivers are described as the "critical marketing targets" and that services specifically for the cognitively impaired should be developed.

Personal accounts of the role of God in health and illness among older rural African American and White residents.

This paper addresses how older rural residents view the relationship between God and both health and illness. We employed semi-structured interviews and qualitative analytical strategies with 15 African Americans residing in predominantly African American communities and 13 Whites living in nearby predominantly White communities, in order to identify similarities and differences in views about a divine other's roles in health and illness. African Americans were more likely than Whites to describe their religious lives in personal terms, in ways suggesting there is a set of religious truths that do not require further investigation or analysis, and in a manner indicating that religious belief permeated their lives. They were also more likely to describe specific role expectations for God in health and illness. The results point to the substantial cultural diversity that exists in small rural areas, and to the need for health care workers to be sensitive to the health-related religious beliefs of patients.

Admission-related migration by older nursing home residents.

OBJECTIVE: To examine recent admissions of older adults to intermediate care facilities in order to identify the factors associated with whether the individual originated in another county, a non-adjacent county, and another state. METHODS: Employing a conceptual framework based upon migration theory and the long-term care decision process and a data set derived from multiple sources, logistic regression was used to examine whether characteristics of the county of residence prior to admission, the admission facility, and the individual are significant net predictors of the three types of mobility. Separate analyses were conducted for married and unmarried individuals. RESULTS: The analytical models tended to have relatively good fit but only moderate predictive accuracy. In general, persons on Medicaid payment status were more likely to move to another county and to a non-adjacent county, whereas Medicaid payment was associated with a lower likelihood of migrating to Virginia from another state. Individuals originating in counties with higher bed rates had lower rates of migration to another county and non-adjacent county, whereas those from counties with higher occupancy rates were more likely to leave their county of origin. CONCLUSION: Examination of factors associated with the distance and patterns of nursing home mobility improves our understanding of the nursing home selection process and helps to illuminate the impact of public policy, market forces, and nursing home staff on who goes where to be admitted to a nursing home.

Preexisting medical conditions in adult day services: an examination of nonmetropolitan and metropolitan admissions.

BACKGROUND: It is not known what health conditions are being managed by day services staff because, to date, there is virtually no research on the types of preexisting medical conditions that clients bring to these community-based settings. Furthermore, it is not known whether or how nonmetropolitan clients differ from their metropolitan counterparts. METHODS: Census data for 1,448 individuals who were admitted to adult day services in Maryland during 1993 were examined. Variables were included for client characteristics, medical diagnoses at admission (based upon ICD-9-CM categories), and adult day center location (metropolitan vs. nonmetropolitan). RESULTS: Persons admitted to nonmetropolitan centers were more likely than those entering metropolitan centers to be diagnosed as having musculoskeletal, respiratory, cardiovascular, and endocrine conditions and as having a malignant neoplasm. Admissions to metropolitan centers were significantly more likely to be diagnosed with Alzheimer's disease. After using multiple logistic regression to control for a number of client characteristics, location of the facility remained significantly associated with all listed admission diagnoses except musculoskeletal conditions. CONCLUSION: Nonmetropolitan centers are caring for a distinctly different type of long-term care client than metropolitan centers, perhaps because few other long-term care options are available to families in sparsely populated settings. The differences in the medical conditions of their clients should affect most aspects of the day services program, including budgets for appropriate professional staff, staff qualifications, resources for client/family education and counseling, and expected outcomes.