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Context: Ethylcellulose is commonly dissolved in a solvent or formed into an aqueous dispersion and sprayed onto various dosage forms to form a barrier membrane to provide controlled release in pharmaceutical formulations. Due to the variety of solvents utilized in the pharmaceutical industry and the importance solvent can play on film formation and film strength it is critical to understand how solvent can influence these parameters., Objective: To systematically study a variety of solvent blends and how these solvent blends influence ethylcellulose film formation, physical and mechanical film properties and solution properties such as clarity and viscosity., Materials and Methods: Using high throughput capabilities and evaporation rate modeling, thirty-one different solvent blends composed of ethanol, isopropanol, acetone, methanol, and/or water were formulated, analyzed for viscosity and clarity, and narrowed down to four solvent blends. Brookfield viscosity, film casting, mechanical film testing and water permeation were also completed., Results and Discussion: High throughput analysis identified isopropanol/water, ethanol, ethanol/water and methanol/acetone/water as solvent blends with unique clarity and viscosity values. Evaporation rate modeling further rank ordered these candidates from excellent to poor interaction with ethylcellulose. Isopropanol/water was identified as the most suitable solvent blend for ethylcellulose due to azeotrope formation during evaporation, which resulted in a solvent-rich phase allowing the ethylcellulose polymer chains to remain maximally extended during film formation. Consequently, the highest clarity and most ductile films were formed., Conclusion: Employing high throughput capabilities paired with evaporation rate modeling allowed strong predictions between solvent interaction with ethylcellulose and mechanical film properties.

This three-part review has been developed following the evaluation of literature where ethylcellulose, methylcellulose, or hypromellose was used to make microcapsules. Parts 1 and 2 of the review are published in separate papers. Part 1 covers the various materials used to formulate microcapsules, and Part 2 covers the various techniques used to make microcapsules. In the current paper, Part 3 covers the end-use applications for which microcapsules are used. Examples of applications to be covered include modified release, improved efficacy and safety, multiparticulate compression, improved processability and stability, and taste- and odor-masking. It is hoped that formulators can use Part 3 to understand the various end-use applications of microcapsules made from these encapsulating polymers. SciFinder was utilized to perform the literature search. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers.

This review highlights references where ethylcellulose, methylcellulose and hypromellose were used to make microcapsules. The review has been divided into three parts. This first part discusses various materials used to formulate microcapsules, such as the three encapsulating polymers as well as protective colloids, plasticizers and surfactants. The second part covers the various techniques used to make microcapsules, such as temperature-induced phase separation, emulsion solvent evaporation, solvent evaporation, film coating, and others. The third part covers the various applications for which microcapsules are used, such as modified release, improved efficacy and safety, taste- and odor-masking, and others. It is hoped that formulators can use Part 1 as a guide to the literature documenting formulation of microcapsules made from these encapsulating polymers. SciFinder was utilized to identify the pertinent literature. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers.

This three-part review has been developed following the evaluation of literature where ethylcellulose, methylcellulose or hypromellose was used to make microcapsules. Parts 1 and 3 of the review are published as separate papers. Part 1 covers the various materials used to formulate microcapsules, and Part 3 covers the various end-use applications for microcapsules. In the current paper, Part 2 covers the techniques used to make microcapsules. Examples of techniques to be covered include temperature-induced phase separation, emulsion solvent evaporation, solvent evaporation, film coating, nonsolvent addition and spray drying. It is hoped that formulators can use Part 2 to understand how to formulate microcapsules using these encapsulating polymers. SciFinder was utilized to perform the literature search. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers.

Purpose: The objective of this study was to investigate the physical stability of micronized powders produced by the spray-freezing into liquid (SFL) particle engineeringtechnology., Materials and Methods: Danazol was formulated with polyvinyl alcohol (MW 22,000), poloxamer 407, and polyvinylpyrrolidone K-15 to form a cosolvent solution that was SFL processed. The dried micronized SFL powders were sealed in glass vials with desiccant and exposed to 25 degrees C/60% RH for 3 and 6 mo, 40 degrees C/75% RH for 1, 2, 3, and 6 mo, and conditions where the temperature was cycled between -5 and +40 degrees C (6 cycles/24 hr) with constant 75% RH for 1, 2, 3 and 4 wk. The samples were characterized by using Karl-Fisher titration, differential scanning calorimetry, x-ray diffraction, specific surface area, scanning electron microscopy, and dissolution testing., Results: Micronized SFL powders consisting of porous aggregates with small-particle domains were characterized as having high surface areas and consisted of amorphous danazol embedded within a hydrophilic excipient matrix. Karl-Fischer titration revealed no moisture absorption over the duration of the stability studies. Differential scanning calorimetry studies demonstrated high degrees of molecular interactions between danazol, PVA, poloxamer, and PVP. Scanning electron microscopy studies confirmed these interactions, especially those between danazol and poloxamer. These interactions facilitated API dissolution in the aqueous media. Powder surface area remained constant during storage at the various stability conditions, and danazol recrystallization did not occur during the entirety of the stability studies. Micronized SFL powders containing danazol dissolved rapidly and completely within 5 min in aqueous media. No differences were observed in the enhanced dissolution profiles of danazol after exposure to the storage conditions investigated. Physically stable micronized powders produced by the SFL particle engineering technology were produced for the purpose of enhancing the dissolution of an insoluble drug., Conclusions: The potential of the SFL particle-engineering technology as a micronization technique for enhancing the dissolution of hydrophobic drugs was demonstrated in this study. The robustness of the micronized SFL powders to withstand stressed storage conditions was shown.

SUMMARY Understanding the mental health needs of lesbian and bisexual (sexual minority) women is an integral part of designing and providing appropriate mental health services and treatment for them. In an effort to understand the mental health needs of sexual minority women who seek community treatment, a chart review was conducted of the 223 lesbian and bisexual women who presented for services between July 1, 1997 and December 31, 2000 at Fenway Community Health in Boston, MA. Data are based on clients' self-reports and clinician assessments of clients' presenting problem, relevant developmental history, prior mental health and substance abuse treatment, current reports of emotional/psychological symptoms, and areas of impaired functioning. Although substance abuse and suicidal ideation were commonly reported problems, other concerns were more frequently reported. High percentages of lesbians and bisexual women reported relationship concerns and lack of adequate social networks; rates of depression and anxiety based on clinicians' assessments were also high. Overall, lesbians and bisexual women did not differ in the issues they brought to treatment or level or types of impairment. Compared with previous community survey samples, however, study participants appeared to be healthier than general, non-clinical samples of self-identified lesbians, possibly reflecting the special characteristics of sexual minority women who seek treatment in specialized community sites such as the Fenway. Although patients who come to these sites may not represent the more general population of sexual minority women, community health centers known to serve lesbian, gay, bisexual and transgender (LGBT) individuals may be fruitful access points for studying the mental health status and treatment needs of sexual minority women.

Micronization is an important procedure used in the pharmaceutical industry to reduce the particle size of active pharmaceutical ingredients (APIs). The spray-drying and milling techniques presently used to micronize drug substances cannot be used to process thermolabile or physically unstable drug substances. Therefore, new micronization techniques, including particle precipitation with supercritical or compressed fluid CO2 and spray-freezing of drug solutions and suspensions into cryogenic gas to produce solid frozen microparticles, are currently being perfected for future use in the pharmaceutical industry. This review highlights the compressed gas and cryogenic liquid technologies being developed as potential solution-based particle formation technologies for drugs that cannot be processed by conventional micronization techniques.

Five commercially available spacers were investigated to determine their influence on the percentage of drug retained in the spacer device, percentage fine particle fraction (FPF), percentage deposited in the induction port, mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). Betamethasone valerate (BMV) and triamcinolone acetonide (TAA) were used as model drugs in the pressurized metered dose inhaler (pMDI) formulations containing the propellant HFA 134a. The BMV was dissolved in an ethanol/HFA 134a system, and the TAA was suspended in HFA 134a using ethanol as a dispersing agent. The metering chamber volume of the valve was either 50 microl or 150 microl. The spacer devices investigated included the ACE, Aerochamber, Azmacort, Easivent, and Ellipse spacers. Each spacer device was attached to an Andersen Cascade Impactor powered by a vacuum pump. Cascade impaction data were used to derive the percentage drug deposited in the induction port, MMAD, GSD, and FPF. The BMV particles emitted from the spacers were finer than the TAA particles because the dissolved drug precipitated as the cosolvent evaporated. The TAA particles had significantly larger MMADs because many undissolved drug particles were contained within each droplet following actuation. After evaporation of the liquid continuous phase, the suspended drug aggregated to form larger agglomerates than those particles precipitated from the BMV pMDI solution droplets. The addition of a spacer device lowered the MMAD to less than 4.7 microm for particles from both the BMV pMDI solution and the TAA pMDI suspension. The addition of a spacer device also lowered the percentage drug deposited in the induction port. The FPF was significantly increased when a spacer device was used. The MMAD significantly decreased when a spacer device was added for the two model drugs when using the 150-microl metering valves, but the difference was not statistically significant when the 50-microl valves were used (P < .05). The GSD was not influenced by the use of a spacer device. The use of a spacer device will enhance pMDI therapy by reducing the amount of drug deposited in the oropharyngeal region, which will lead to fewer instances of local and systemic side effects. In addition, the spacer devices investigated will allow a higher dose of drug to reach the deep lung, which may permit the use of lower dosage regimens with increased therapeutic efficacy.

The solubility of prednisone, hydrocortisone 21-acetate, hydrocortisone, dexamethasone, betamethasone 17-valerate, and danazol in hydrofluoroalkane (HFA) 134a and HFA 227 was determined at 5 degrees C and 25 degrees C. It was found that the solubility of steroid in HFA propellants was related to the melting point and the lipophilicity of the steroid. The solubility of the steroids in the binary system of HFA propellants and ethanol also was investigated in the study. Ethanol significantly increased the solubility of the steroids in HFA propellant. The magnitude of increase was related to the solubility of the corresponding steroid in ethanol alone.