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Tuesday, 02 April 2013 14:43

Film preparations for oral drug delivery

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Introduction

Oral films have gained interest in the last couple of years. Films for oral application offer an interesting new approach for drug administration. Active pharmaceutical ingredients (API) can be implemented in thin-sheeted polymer film matrices. These dosage forms are intended to be placed in mouth to dissolve in the saliva without the need of additional liquid and without swallowing of a solid dosage form.

 

Definition - Oromucosal Film Preparations

Most recently, films for oral drug delivery became part of the European Pharmacopoeia, edition 7.4 [1]. They are subordinated to the monograph 'oromucosal preparations'. Films are either described as fast-dissolving 'orodispersible films' or 'mucoadhesive / buccal films', which are intended to be attached to oromucosal sites.

Application

Oral film preparations are useful dosage forms for local drug administration, but also for systemic drug delivery (Fig. 1). A bioadhesive film can be placed on the oromucosal tissue. By film dissolving the API is released onto, into or through the mucosa. Assuming absorption of the API, action may take place by avoiding the gastrointestinal and the enterohepatic route. The use of multiple layers in a mucoadhesive film preparation is reasonable, when pursuing the setup of a multifunctional system (Fig. 2). However, films can also function as alternative per oral administration. A fast-dissolving orodispersible film that is placed on the tongue disintegrates within seconds. Subsequently, the released API is intentionally or incidentally swallowed with the saliva [2].

Manufacturing of Films

The most popular approach to manufacture films is the solvent casting method. Viscous solutions made of polymers (e.g. cellulose derivatives, polysaccharides) and dissolved or suspended API are cast on a film application apparatus by the help of a coating knife [3]. After drying and solvent evaporation, films can be cut into single doses [4]. Wet and melt extrusion offer an alternative way of manufacturing. Polymer mass is pressed through a die, which has a laminar opening at best, to obtain film stripes. An alternative and flexible manufacturing method of drug-loaded film preparations are drug printing methodologies, such as Flexography [5] and ink-jet printing [6].

Challenges in Characterisation

Novelty of the pharmacopoeial monograph leads to a lack in characterization requirements. According to the Ph. Eur. only adequate drug release and mechanical strength are required to be tested without providing detailed instructions. Previous research projects already focused on new characterization methods for films [5]. Other than for orodispersible tablets, there is no time restriction for film disintegration so far. Even if the monograph describes mucoadhesive dosage forms, there is no standardized method to proof bioadhesion appropriately. As oromucosal film preparations are intended to dissolve in mouth, taste of the formulation presents another challenge in dosage form development. Therefore, masking the taste of a bitter drug can be achieved by applying different taste-masking strategies. Taste-masking effects may be assessed in-vitro by the use of electronic taste sensing systems [2, 7].

Oromucosal films are an attractive type of formulation for personalised medicine.

Future Work

The research on oromucosal film preparations in Düsseldorf is further focusing on the development of new manufacturing and improved characterization methods for film dosage forms. The professional expertise in film manufacturing was recently expanded to optimize the attributes of film preparations with suspended APIs, gastro intestinally unstable APIs and multiple layered oromucosal films.

References

[1] European Pharmacopoeia Commission. Oromucosal Preparations. In European Pharmacopoeia – edition 7.4; European Directorate for the Quality of Medicines (EDQM): Strasbourg, France, 2012; pp. 4257–4259.

[2] Preis, M., Pein, M., & Breitkreutz, J. (2012). Development of a Taste-Masked Orodispersible Film Containing Dimenhydrinate Pharmaceutics, 4 (4), 551-562 DOI: 10.3390/pharmaceutics4040551

[3] Garsuch V, & Breitkreutz J (2010). Comparative investigations on different polymers for the preparation of fast-dissolving oral films. The Journal of pharmacy and pharmacology, 62 (4), 539-45 PMID: 20604845

[4] Hoffmann EM, Breitenbach A, & Breitkreutz J (2011). Advances in orodispersible films for drug delivery. Expert opinion on drug delivery, 8 (3), 299-316 PMID: 21284577

[5] Janßen E.M., Schliephacke R,, Breitenbach A,, & Breitkreutz J (2013). Drug-printing by flexographic printing technology—A new manufacturing process for orodispersible films International Journal of Pharmaceutics, 441 (1-2), 818-825 : 10.1016/j.ijpharm.2012.12.023

[6] Genina N, Janßen EM, Breitenbach A, Breitkreutz J, Sandler N, Evaluation of different substrates for inkjet-printing of rasagiline mesylate substrates, European Journal of Pharmaceutics and Biopharmaceutics, submitted (2013).

[7] Garsuch V, & Breitkreutz J (2009). Novel analytical methods for the characterization of oral wafers. European Journal of Pharmaceutics and Biopharmaceutics, 73 (1), 195-201 PMID: 19482082

[8] Woertz K, Tissen C, Kleinebudde P, & Breitkreutz J (2011). Taste sensing systems (electronic tongues) for pharmaceutical applications. International journal of pharmaceutics, 417 (1-2), 256-71 PMID: 21094230

PSSRC Facilities

The research groups of Professor Jörg Breitkreutz and Professor Peter Kleinebudde in Düsseldorf are working on solid dosage forms and pharmaceutical processes like roll compaction / dry granulation, extrusion and coating. Drug development for neglected patients such as pediatric and geriatric subpopulations are of key interest. A major topic is the development and characterization of new orodispersible film preparations, which is performed in the focus groups 'Coating and Films' chaired by Dr. Klaus Knop and 'Advanced Analytics' chaired by Dr. Miriam Pein.

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