Film Dosage Form Research Articles

Control of Drug Dissolution Rate from Film Dosage Forms Containing Valsartan.

Film dosage forms (FDs) containing valsartan (VST), a popular antihypertensive drug, were prepared using a casting method with sodium alginate and other polysaccharides as the film base. Drug dissolution profiles of the FDs were investigated in limited medium. The FDs were 170–200 μm thick and were easy to handle. All FDs immediately swelled and disintegrated in the medium. About 23% of the VST incorporated into the FD prepared with 1.5% sodium alginate dissolved at 5 min. The initial dissolution rate of VST increased upon the addition of chitosan to the film base; this effect was not observed in the case of chitin. On the other hand, the rate apparently decreased upon modification with alginic acid. In addition, the solubility of VST in the dissolution medium was changed by the addition of chitosan or alginic acid. FDs prepared with polysaccharides are useful for simplifying the administration of drugs to patients, and the drug dissolution rate from FDs can be controlled by modification.

Cyclodextrin-Modified Film Dosage Forms for Oral Candidiasis Treatment

Oral candidiasis is a common disease in patients with dry mouth. In this study, film dosage forms (FD) incorporating miconazole nitrate, an antifungal agent, were prepared with water-soluble polysaccharide and cyclodextrin (CD). The dissolution profiles of the drug from the FDs were investigated in limited dissolution medium. Soft films were obtained from sodium alginate containing 0.5% α-CD, β-CD, or γ-CD. Most FDs were easy to handle, though the film tearing resistance was lower than that of CD-free FDs. Addition of CD to the FD accelerated the drug dissolution rate. Interestingly, this phenomenon was also observed in FDs prepared with pullulan. In contrast, acceleration of the drug dissolution rate was not observed when CD polymer was added to the base solution. The initial drug dissolution rate was controllable by the amount of CD added to the FD. Therefore, FDs prepared with these materials are useful to treat oral candidiasis in patients with dry mouth syndrome.

Development and characterization of a solid dispersion film for the vaginal application of the anti-HIV microbicide UAMC01398

The purpose of this work was to design and evaluate a vaginal film delivery system for UAMC01398, a novel non-nucleoside reverse transcriptase inhibitor currently under investigation for use as an anti-HIV microbicide. UAMC01398 (1mg) films consisting of hydroxypropylmethylcellulose (HPMC) and polyethylene glycol 400 (PEG400) in different ratios were prepared by solvent evaporation. Based on its flexibility, softness and translucent appearance, the 30% PEG400 and 70% HPMC containing film was selected for further assessment. The vaginal film formulation was fast-dissolving (<10min in 1mL of vaginal fluid simulant), stable up to at least one month and safe toward epithelial cells and lactobacilli. Furthermore, formulating UAMC01398 into the film dosage form did not influence its antiviral activity. Powder X-ray diffraction revealed the amorphous nature of the UAMC01398 film, resulting in enhanced compound permeation across the epithelial HEC-1A cell layer, presumably owing to the induction of supersaturation. The in vivo vaginal tissue uptake of UAMC01398 in rabbits, as measured by systemic concentrations, was increased compared to the previously established non-solubilizing gel (significant difference) and sulfobutyl ether-β-cyclodextrin (5%) containing gel. To conclude, we identified a film formulation suitable for the vaginal delivery of UAMC01398.

Development of Film Dosage Forms Containing Miconazole for the Treatment of Oral Candidiasis

Film dosage forms (FDs) containing miconazole (MCZ) for the treatment of oral candidiasis were prepared using water-soluble polysaccharides, and the dissolution profiles of MCZ from the FDs were investigated. In addition, the forms were modified by the addition of a surface active agent to accelerate the drug dissolution rate. Circular films incorporating MCZ were obtained using each polysaccharide. Most FDs were easy to handle and resistant to tearing. No diffraction peaks were observed in the X-ray diffractograms of FDs. FDs prepared with sodium alginate or pullulan immediately swelled and disintegrated in aqueous medium, whereas MCZ incorporated in the FD gradually dissolved. A marked acceleration in the MCZ dissolution rate was observed when FD was prepared with polysaccharide containing a surfactant. These results confirmed that modified FDs are useful for treating localized conditions in the oral cavity, such as oral candidiasis, and that FDs can simplify the administration of drugs to patients.

Development of film dosage form containing allopurinol for prevention and treatment of oral mucositis.

Film dosage forms (FDs) containing allopurinol (AP) were prepared using a casting method with water-soluble polysaccharides, such as sodium alginate (ALG), and the release profile of AP from FDs was investigated in limited dissolution medium. Some ALGs were able to form FDs incorporating AP, and the thickness was about 50 μm. All FDs were easy to handle, though the rheological properties varied with ALG species. AP was homogenously present throughout the FDs and was released with disintegration in 10 mL of physiological saline. These results confirmed that FDs are useful for preventing or treating localized problems in the oral cavity, such as mucositis. FDs are also useful for administering drugs to cancer patients receiving chemotherapy and/or radiotherapy.

Preparation and Characteristics of Film Dosage Form Natural Polysaccharides

We investigated preparation of film dosage form (FD) from natural polysaccharides using the casting method without organic solvents, heating or pH control. Ferulic acid (FA) and catechin were employed as model compounds incorporated in the FD, and the release profile of each compound from the form was investigated in the limited medium. Film formation was affected by the addition of the model compound to the polysaccharide solution. Rigid FD was obtained with 2% low-molecular-weight alginate (L-ALG; thickness, 65 µm), and it hardened after the addition of 0.5% polygalacturonic acid, although the thickness of the film did not change. The FDs immediately released the model compound, and the forms dissolved in phosphate-buffered saline. FD modification did not affect the FA release rate except in the early stage. FD would be a useful dosage form, especially for preventing or treating localized problems in the oral cavity.

天然多糖類を用いて調製したメトロニダゾールフィルムの特性

Film dosage forms containing metronidazole (MZ) were prepared from natural polysaccharides, such as pullulan (PUL) or sodium alginate (ALG), without heating or controlling the pH. The release profiles of MZ from the films were investigated. In the absence of a drug, the casting method resulted in the polysaccharide forming a circular film, and the presence of MZ affected film formation. The thickness of the film was controllable by adjusting the concentration of ALG, and regular unevenness was observed on the surface of film. The film prepared with PUL or ALG readily swelled in dissolution medium, and released MZ with disintegration. The films prepared from the polysaccharides could be promising candidates as dosage forms containing MZ, and would be expected to show drug dissolution in the surface of skin.

Pharmaceutical Rapidly Disintegrating Film Dosage Form in Oral Cavity

Pharmaceutical Rapidly Disintegrating Film Dosage Form in Oral Cavity

Effect of Low-Molecular-Weight .BETA.-Cyclodextrin Polymer on Release of Drugs from Mucoadhesive Buccal Film Dosage Forms

We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.

Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug

The aim of the present work was to design a film dosage form for sustained delivery of ipriflavone into the periodontal pocket. For this purpose, monolayer composite systems made of ipriflavone loaded poly( d, l-lactide-co-glycolide) (PLGA) micromatrices in a chitosan film form, were obtained by emulsification/casting/evaporation technique. Multilayer films, made of three layers of polymers (chitosan/PLGA/chitosan), were also prepared and compared to monolayer films for their “in vitro” characteristics. Morphology and physico-chemical properties of the different systems were evaluated. The influence of pH, ionic strength and enzymatic activity on film degradation, was also investigated. Significant differences in swelling, degradation and drug release were highlighted, depending on film structure and composition. In vitro experiments demonstrated that the composite micromatricial films represent a suitable dosage form to prolong ipriflavone release for 20 days.

Development of Polymer Film Dosage Forms of Lidocaine for Buccal Administration: II. Comparison of Preparation Methods

In previous studies, we prepared film dosage forms of lidocaine (LC) with hydroxypropylcellulose (HPC) as a film base using the solvent evaporation (SE) method. However, from the viewpoint of environmental issues, a reduction in organic solvent use in pharmaceutical and other industries is required. In this study, we prepared the LC films by direct compression of the physical mixture (DCPM method) and direct compression of the spray dried powder (DCSD method). Magnesium stearate, which was required as a lubricant for direct compression, showed no effect on the LC release rate. The LC release rate (%/h) was independent of the compression pressure, but a higher pressure was preferable to easily remove the film from the punches. An increase in the film weight decreased the LC release rate expressed in %/h, whereas no significant effect of film weight was observed on the LC release rate from unit surface area expressed in mg/h/cm2. The LC release rate (%/h) was independent of the LC content, suggesting that the LC release rate (mg/h) can be quantitatively controlled by changing the LC content in the formulation. The LC release rate and penetration rate were affected by the preparation method; that is, DCPM method < DCSD method < SE method. The LC penetration rates through excised hamster oral mucosa were linearly correlated to the release rate of un‐ionized LC, which was estimated by the LC release rate multiplied by the un‐ionized fraction of LC for the HPC film dosage form. ©2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2424–2432, 2002

Development of polymer film dosage forms of lidocaine for buccal administration: I. Penetration rate and release rate

We examined the penetration rate of lidocaine (LC) through excised oral mucosa from hamster cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose (HPC) as a film base. Addition of glycyrrhizic acid (GL) to the HPC films increased the LC release rate almost GL-content-dependently, while an optimum GL content was observed for the LC penetration rate. No LC penetration was observed from an acidic aqueous solution (pH 3.4) of LC, suggesting only unionized LC can substantially penetrate through the mucosa. A significant relationship between the penetration rate of LC and the release rate of unionized LC was found, suggesting that the in vitro dissolution study is a useful tool to predict the penetration rate taking the unionized drug fraction into consideration.

Improvement of Release Rate of Diclofenac from Oro-Muco-Adhesive Film Dosage Form by Incorporating Electrolytes and Its Effects on Mucosal Absorption

Improvement of Release Rate of Diclofenac from Oro-Muco-Adhesive Film Dosage Form by Incorporating Electrolytes and Its Effects on Mucosal Absorption

Regional variation in oral mucosal drug absorption: permeability and degree of keratinization in hamster oral cavity.

The regional permeability of oral mucosa to salicylic acid was investigated in vivo in hamsters along with histological variations, especially the degree of keratinization. Histological sections from six regions, i.e., sublingual mucosa, buccal mucosa, dorsum of tongue, ventral surface of tongue, labial mucosa, and cheek pouch mucosa, were prepared to assess the degree of keratinization. The area under the plasma concentration-time curve of salicylic acid following the administration of salicylic acid to the oral mucosa with a film dosage form and the thickness of stratum corneum of each site were in inverse proportion to each other, suggesting that the stratum corneum layer represents the principle barrier to drug absorption.

Application of propranolol to the keratinized oral mucosa: avoidance of first-pass elimination and the use of 1-dodecylazacycloheptan-2-one (Azone) as an absorption enhancer of bioadhesive film-dosage form.

The bioavailability of propranolol applied to the oral mucosa was examined in the hamster. The capacity of hamster cheek pouch, used as a model of keratinized oral mucosa, to metabolize propranolol in vitro is enormously lower than that of the liver. Significant amounts of propranolol absorbed from the small intestine were metabolized to naphthoxylactic acid and 4-hydroxypropranolol (4HP) during the passage through the intestinal wall, and then the greater portion of unchanged propranolol and almost all 4HP were subsequently metabolized by hepatic first-pass elimination in vivo. The systemic bioavailabilities of propranolol after the intra-small-intestinal loop and the intra-cheek-pouch administrations were 8.4% and 88.5%, respectively. The bioavailability of propranolol was improved further (to 97.1%) by a 1-h pretreatment of the cheek pouch with 5% 1-dodecylazacycloheptan-2-one (Azone)-emulsion. Bioadhesive film-dosage forms of propranolol were prepared with hydroxypropylcellulose. Both the in vitro permeation and the in vivo absorption of propranolol across the cheek pouch were enhanced by the incorporation of Azone to the film-dosage form.