The design of efficient films as carriers for drug delivery requires a proper selection of the polymer and excipients used for their fabrication because they affect the ability of the films to swell, degrade and modulate the release of the therapeutic molecule.
The reduced size and thickness as well as the large number of excipients used in the film formulation can severely limit the loading levels capacity of the dosage form. Similarly, uncontrolled crystallization of drug upon fabrication or storage is frequently evidenced in this type of delivery systems, especially when a high dose of the active molecule is included. High concentration of a drug can promote the formation of fractal-shaped aggregates . The presence of these aggregates, commonly observed with lipophilic molecules, can adversely affect the uniformity of the resulting film as well as drug release kinetics and the physical stability during storage.
From a pharmaceutical perspective, the investigation of strategies aimed to avoid drug nucleation and crystal growth as well as the inhomogeneous distribution of the therapeutic molecule deserve special attention as these aspects are of critical importance for the development of commercially viable formulations.
An interesting strategy may be represented by the use of a functional excipient, such as cyclodextrins, which should help maintaining low amount of plasticizer avoiding problems related to drug solubility and crystallization. In particular, the hydroxypropyl-beta-cyclodextrin (HPbCD) may be extremely useful due to its high solubility, good complexing properties and absence of irritant or toxic effects
This project is aimed at developing a mucoadhesive film formulation for topical buccal administration of therapeutic drugs (characterized by low solubility and poor wettability) by investigating the influence of drug complexation with HPbetaCD on mechanical properties as well as dissolution properties and release rate from the buccal film.
During the past several years, pharmaceutical research has showed a growing interest in developing new dosage forms for existing drugs. Reformulation of old active pharmaceutical ingredients into new dosage forms meets the need for alternative delivery routes as well as targeted and modified or sustained drug release. Research in the oral drug delivery segment has led to development of drug formulations from simple conventional tablets/capsules to modified release tablets/capsules to oral disintegrating drug delivery systems. In this context, innovative thin films have recently gained a lot of attention as a non-invasive route for drug delivery. These systems represent the most advanced and well-appreciated solid dosage forms for oral administration of drugs, as they ensure great patient compliance, especially among geriatric and pediatric patients having difficulty in swallowing conventional tablets or capsules. Dysphagia is a problem commonly found among all aged people, which has led to great increase in request for alternative and versatile formulations, like polymeric strips.
Approximately 50% of population tend to avoid taking oral solid dosage preparations due to fear of choking. In this context, thin films provide an appealing alternative for administering drugs in a precise and uniform way and, at the same time, overcome various problems related to swallowing. As a result, the demand for developing thin-film technologies has been increasing. Many companies are investing in OTF technologies as they offer a versatile platform able to develop both local or systemic pharmacological effects, as well as fast or sustained drug release. Different types of oral thin films (e.g. orodispersible, sublingual, buccal) may be developed in response to specific needs. This technology can also be used as an alternative platform for molecules that undergo first pass metabolism and for delivery of peptides. In fact, in addition to low molecular drugs, several hormones and vaccines are also being formulated as oral thin films with the aim of providing improved patient compliance. All that considered this technology might open up exciting opportunities for product development by transforming conventional dosage forms into oral thin films.
Several OTFs have been already approved and are now commercialized in US, EU and Japan. Most of them are over-the-counter products, however also prescription OTFs are available on the market. These approved films have potential to succeed on other oral dosage forms of the same drugs. It seems that the value of the overall OTFs market will grow significantly.
Much work has already been done in this field, however further efforts are still needed to take full advantage of OTFs potential in drug delivery. In particular, ongoing research is trying to extend the dissolvable film technology to more complicated systems for modified or controlled drug release. In fact, while the development of OTFs for fast drug release is relatively not complicated, more hurdles are found in the design of strips able to modify or control the release rate of a drug embedded in the polymeric matrix. In this sense, there is much interest in the design of flexible, elastic films possessing good bioadhesive properties in relation to their ability to remain in the oral cavity for an extended period of time and ensure prolonged drug release to get adequate therapeutic response. In this context, it becomes of primary importance the possibility to achieve high drug loadings in the reduced surface area of a polymeric thin film, while avoiding possible crystallization phenomena of the drug. To this end, the project primary aims to evaluate different integrated approaches in order to find a widely applicable strategy for fabrication of homogeneous polymer-based thin films for oral drug delivery.