Development of orodispersible polymer films containing poorly water soluble active pharmaceutical ingredients with focus on different drug loadings and storage stability.

The aim of this work was the development of orodispersible films containing different film forming polymers with focus on different drug loadings of two poorly water soluble APIs. Furthermore, physical stability of films was examined at two different storage conditions. Loperamide hydrochloride (LPH) and ibuprofen (IBU) were used as model drugs. Hydroxypropyl methylcellulose (HPMC) and three different types of hydroxypropyl cellulose (HPC) were used as film forming polymers. Suspensions were characterized with respect to their viscosity and particle sedimentation and films regarding their content uniformity, thickness, mass and stability. Principal component analysis (PCA) was used to evaluate the correlation between the wet film thickness, dry film thickness, mass of the films, API fraction in the suspension and the viscosity of the suspensions. The viscosity of the suspensions was dependent on the drug load and the polymer fraction but less so on the type of the utilized polymer. A correlation between the wet film thickness, the solid fraction and the mass of the films was established with an increase in mass by increasing the wet film thickness or the solid fraction. Films containing 50 mg IBU/6 cm(2) film led to acceptable films. Storage experiments did not lead to an AV below 15 in all cases after storage for three and six months, attributed to the storage conditions and the quality of the films. Nevertheless, the development and production of flexible and homogeneous films of LPH and IBU was successfully achieved.

Development of orodispersible polymer films with focus on the solid state characterization of crystalline loperamide.

The formulation of active pharmaceutical ingredients (API) as orodispersible films is gaining interest among novel oral drug delivery systems due to their small size, enhanced flexibility and improved patient compliance. The aim of this work was the preparation and characterization of orodispersible films containing loperamide hydrochloride (LPH) as model drug. As loperamide hydrochloride is poorly soluble in water it was used in crystalline form with a loading of 2mg/6cm(2) film. Hydroxypropyl methylcellulose (HPMC) and different types of hydroxypropyl cellulose (HPC) in different concentrations were used as film forming polymers whereas arabic gum, xanthan gum and tragacanth served as thickening agents. Films were characterized with respect to the content uniformity, morphology, thermal behavior and crystallinity. Suspensions were investigated regarding their viscosity using a rotational rheometer and the crystal structure of the Active Pharmaceutical Ingredient (API) was analyzed using polarized light microscopy. The development of flexible, non-brittle and homogeneous films of LPH was feasible. Two polymorphic forms of LPH appeared in the film formulations dependent on the utilized polymer. While in presence of HPMC the original polymorphic form I remained stable in suspension and films, the polymorphic form II occurred in presence of HPC. Both polymorphic forms were prepared separately and a solid state characterization was performed. Polymorph I showed isometric crystals whereas polymorph II showed needle shaped crystals. Tragacanth was able to prevent the transformation to polymorph II, if it was dissolved first before HPC. When HPC was added first to the suspension, the conversion to form II occurred irreversibly also after further addition of tragacanth.

Design and evaluation of bilayered buccal film preparations for local administration of lidocaine hydrochloride.

Bilayered oromucosal film preparations (buccal films) offer a promising way to enable drug administration via the oral cavity. Adding a non-soluble or slowly eroding/dissolving backing layer to a mucoadhesive drug-loaded layer enables unidirectional drug delivery. The aim of this study was to investigate different approaches to the manufacture of bilayered films and to examine their properties by applying different characterization methods including an optimized experimental setup for the study of drug release from bilayered films. A solvent suitability study was performed screening over 15 polymers with respect to their feasibility for viscous film formation for film preparation by solvent casting method. Two methods (double-casting and pasting) were found as suitable methods for bilayered film manufacturing. Results from drug release experiments indicated that slowly eroding hypromellose backing layer films revealed the best shielding of the drug-loaded layer to enable unidirectional drug release. In summary, manufacturing of bilayered films using the described methods was feasible. Furthermore, the use of an optimized experimental setup for drug dissolution studies enabled monitoring of drug release without delays in sampling.

Assessment of test methods evaluating mucoadhesive polymers and dosage forms: an overview.

Oral mucoadhesive preparations have gained increasing importance in the last decades, by reason of numerous advantages like easy application, discrete handling and no swallowing of the drug product. Pharmacopoeial methods to study mucoadhesion are not available so far, despite the new monograph for oromucosal preparations is valid since the European Pharmacopoeia 7.4 (2012) including a chapter on mucoadhesive preparations. Several mucoadhesion test methods are reviewed concerning the applicability for various polymers, different drug dosage forms and comparability of experimental set-ups. Different test methods and experimental set-ups lead to huge differences regarding the results.

Oromucosal film preparations: classification and characterization methods.

INTRODUCTION: Recently, the regulatory authorities have enlarged the variety of 'oromucosal preparations' by buccal films and orodispersible films. Various film preparations have entered the market and pharmacopoeias. Due to the novelty of the official monographs, no standardized characterization methods and quality specifications are included. AREAS COVERED: This review reports the methods of choice to characterize oromucosal film preparations with respect to biorelevant characterization and quality control. Commonly used dissolution tests for other dosage forms are not transferable for films in all cases. Alternatives and guidance on decision, which methods are favorable for film preparations are discussed. Furthermore, issues about requirements for film dosage forms are reflected. EXPERT OPINION: Oromucosal film preparations offer a wide spectrum of opportunities. There are a lot of suggestions in the literature on how to control the quality of these innovative products, but no standardized tests are available. Regulatory authorities need to define the standards and quality requirements more precisely.