Sudhakarrao Naik Instituted of Pharmacy, Pusad Maharashtra, India 445204
Film forming sprays present a promising approach for topical drug delivery. offering advantages such as enhanced bioavailability, reduce irritation, and accelerated wound healing. These systems form thin, transparent films on the skin, allowing for sustained release of active ingredients. Both natural and synthetic polymers with film forming properties can optimize drug delivery through these systems. Film forming solution utilized various components including drugs, solvent systems, polymers, and penetration enhancers prepared invisible drug depots in the skin for gradual absorption. Plasticizer are incorporated to enhance film flexibility and strength, with considerations for compatibility and skin permeability. Evaluation parameters like drying time and stickiness influence the formulations efficacy and patient comfort. In vitro diffusion studies provide insights into drug permeation properties. The film forming system shows potential for topical and transdermal drug delivery, but further research is required to fully establish its efficacy efficiency. This novel technology holds promise for future advancement in topical drug delivery applications.
The skin is a very important route for the dermal or transdermal delivery of pharmaceutically active substances. Film forming polymeric solutions are a novel approach in this area that might present an alternative to the conventional dosage forms used on the skin, such as ointments, creams, gels or patches. The polymeric solution is applied to the skin as a liquid and forms an almost invisible film in situ by solvent evaporation.1 The skin is the most readily accessible organ of the body and acts as a barrier against the micro and macromolecules of the environment because of its low permeability to such substances. The skin of an average adult body has approximately 2 m2 surface area and it receives about one-third of the total blood circulating throughout the body. Percutaneous absorption of drug through skin mainly occurs via stratum corneum. Stratum corneum is made up of dead, keratinized epidermal cells having thickness of 10 µm and acts as a barrier for permeation of drugs. Therefore transport of drug molecules across the skin is difficult.2 Fungal infection, commonly known as “mycosis”, is a skin infection caused by a fungus. Fungi, which dwell in the earth, on plants, household surfaces, and skin, can trigger skin problems, such as rashes or bumps. Fungi typically grow in moist parts of the body such as between the toes, in the vaginal area, and beneath the breasts, where They can cause skin irritation, scaling, redness, itching, swelling, or blister formation.3 Dermatophytes (such as Epidermophyton, Microsporum, and Trichophyton) and yeasts (such as Candida or Malassezia furfur) cause most common fungal skin diseases. These fungi reside Only in the outermost layer of the epidermis (Stratum corneum) and do not penetrate into deeper layers.4 In topical spray, a polymeric solution of the drug is sprayed over the intact skin to get a sustained release of the drug from the polymeric matrix in which the drug is in dissolved form. The drug diffuses slowly, through the polymer matrix as the organic solvent vehicle evaporates and passes through the skin barrier. The type of nozzle, the pressure applied on the spray, the size of the aperture, and the nature of the liquid are major factors that influence the spray ability of film-forming solutions (FFS). The pH, viscoelastic, in situ and thermal-sensitive properties of FFS are essential to study and to determine various aspects required to be considered while selecting solvents, polymers, and other excipients .5 Film forming system (FFS) is a novel approach which can be used as an alternative to conventional topical and transdermal formulations. It is defined as non-solid dosage form that produces a film in situ, i.e. after application on the skin or any other body surface. These systems contain the drug and film forming excipients in a vehicle which, upon contact with the skin, leaves behind a film of excipients along with the drug upon solvent evaporation. The formed film can either be a solid polymeric material that acts as matrix for sustained release of drug to the skin or a residual liquid film which is rapidly absorbed in the stratum corneum.1
Mechanism of Film Formation and Permeation
An FFS is a drug delivery system in the form of a sprayed solution that will form a film when it contacts the target therapeutic site by utilising the polymer as a matrix for film formation.6,7,8 After forming the film, the drug release process is similar to a patch, in which the polymer matrix containing the drug will release it in a sustained Fashion.9 However, in contrast to topical patches and other topical preparations, films form following the pattern of the skin or wound since deep indentations can be exposed to small droplets of the film-forming solution (see Figure 1). of course, this greatly facilitates drug access to the target tissue. In a film-forming spray, drug dosages can also be adjusted based on the volume of solution per spray so that systemic or local effects can be controlled. An FFS also provides an even distribution of drugs and spreads well. Ease of use can also increase patient compliance.6,7,10 The thin film is easy to wash away with water.6,11 This thin and non-sticky film also increases patient comfort during activities compared to using patches, ointments, gels, etc. Because these have a rough and sticky texture when applied.12,13 The thin film also facilitates the permeation of wound moisture so that the balance can be maintained. Inappropriate wound humidity can cause infection or irritation, as happens with the use of patch preparations.14,15 In formation of droplets, the film-forming solution is sprayed using any kind of sprayer. Each sprayer has different specifications and intended uses, but has specific potential in medical applications. The following is an explanation of several types of sprayers that have the potential to be used as drug delivery devices in film-forming systems.
Fig. No.1 Mechanisms of Film Forming Spray[16]
Factors affecting Drug penetration in Dermal Delivery
A Physiological Factors:
B. Physicochemical factors:
Classification of Topical Drug Delivery Systems[17]
|
Sr. No |
Drug Delivery Systems |
Examples |
|
1. |
Solid preparation |
Topical powders, Plasters, Ointments, poultices |
|
2. |
Semi-solid preparation |
Creams, poultices, Gels, pastes |
|
3. |
Liquid preparation |
Liniments, Solutions, tinctures, emulsions, suspensions, paints |
|
4. |
Miscellaneous preparation |
Transdermal drug delivery systems, Tapes and Gauzes |
Comparison of Topical Drug Delivery Systems
FFS form an intermediate between the transdermal patches and semisolid dosage forms. Thus, exhibiting the advantages of both systems. Table 1 summarizes the superiority of film forming systems over patches and ointments. Fig.2 depicts the drug permeation pattern of all the three systems. In case of transdermal patches the drug is stored in a reservoir from which the drug release occurs slowly and the drug is absorbed into the capillaries from where it is transported to systemic circulation or it is formulated as a topical patch so as to penetrate the skin to reach the target tissue for localized action. Drugs incorporated into semisolids show their activity on the skin surface or penetrate into skin layers to reach the site of action but systemic delivery of drugs is limited due to various factors. Film forming systems can function as both semisolids and patches and can provide topical as well as transdermal delivery as desired.
Table no. 1[18]
|
|
Patches |
Film Forming System |
Semisolids |
|
Visual appearance |
Highly visible |
Almost invisible |
Visible |
|
Occlusive properties |
Non-sticky, non-greasy |
Non-sticky, non-greasy |
Sometimes sticky, greasy |
|
Administration |
Convenient |
Convenient |
Sometimes messy |
|
Dose adjustment |
Low |
High |
High |
|
Dosing Frequency |
1-7 d |
1-2 d |
1 d or less |
|
Sustained release |
Yes |
Yes |
No |
|
Occlusive properties |
Yes |
No |
No |
|
Wipe off resistance |
Yes |
Yes |
No |
|
Residual remains |
Possible |
No |
No |
Fig. No.2 Release profile of the topical and transdermal drug delivery systems[19]
Polymers Used in Film-Forming Sprays
Polymers play a significant role in the success of FFS preparations. Aside from being a drug release controller, polymers also act as the film-forming base. Polymers can also prevent the transformation of molecules, such as the formation of unexpected crystals.16 General considerations in the selection of polymers are its ease of being washed away by water, stability, biodegradability, and non-irritating properties.17 Polymers Used in FFS can be natural or synthetic as long as they have in situ gel or viscoelastic properties. Polymers that have thermo-sensitive properties will form a solution at room temperature and turn into a gel when they are exposed to the body temperature, while those that have pH-sensitive properties will form a solution at a certain pH and turn into a gel if the pH of the system Changes. Viscoelastic polymers start at a thick consistency but can become elastic when placed under pressure (sprayed) and return to a thick consistency after the pressure is removed.18
Film Forming Formulations
Spray/ Solution
Film forming solutions and sprays is an attractive approach in transdermal dosage form. In this the polymeric solution is applied to the skin as a liquid or sprayed on the skin and forms an almost transparent film by solvent evaporation.19 The film forming sprays/solutions are made up of four main components – drug, solvent systems i.e. volatile and non-volatile vehicles, polymers and penetration enhancers. The non-volatile component present in the solvent system prevents the drug from precipitating in solution when the volatile solvent component evaporates. The non-volatile component is chosen such that it itself partitions rapidly into the stratum corneum and also aids in partitioning of the drug into the stratum corneum, as well as increases drug diffusivity by disrupting the ordered intercellular lipids and enhance permeation. This type of delivery system creates an invisible depot of drug in the stratum corneum from which the drug can be slowly absorbed into the systemic circulation. Thus a sustained and enhanced permeation of drug across the skin can be achieved following once a day application.20,21 The formulation preparation involves addition of the polymer to the vehicle and stirring of the solution overnight to ensure complete dissolution of the polymer. Once a clear polymeric solution is obtained other optional excipients such as cross linker or plasticizer are added. After addition of all excipients the solution is stirred for 24 h.22 For the physical stability of the API, the polymers are chosen such that they function as anti-nucleating agents and crystallization inhibitors which prevent crystallization of drug even after solvent evaporation, e.g. polyvinyl pyrrolidone, polyethylene glycol, hydroxyl propyl methyl cellulose.
Components of Film Forming Systems
Drug
For transdermal application of film forming systems, the drugs need to have suitable properties which are independent of the dosage form. Generally the drugs which are applicable to these systems are highly potent which permeate the skin rapidly, which cause no skin irritation and which are relatively stable to the enzymes present in the epidermis. Other properties of the drug like partition coefficient dictate the pathway a drug will follow through the skin. Second, the molecular weight of drug is an important factor in drug permeation as small molecules cross human skin than large molecules. The ideal properties of the drug suitable for transdermal drug delivery system are listed in.
Table 2. Ideal Properties of Drug for Transdermal Delivery
|
Parameter |
Properties |
|
Dose |
<10 mg/day |
|
Half life |
10 h or less |
|
Molecular weight |
<500 Dalton |
|
Partition coefficient Log P (octanol/ water) |
Between 1 and 3 |
|
Skin reaction |
Non irritating and non-sensitizing |
|
Oral bioavailability |
Low |
Polymers
Polymers are the foundation of the FFS and a variety of polymers are available for the preparation of these systems. In order to achieve the desired film properties, these polymers can be used alone or in combination with other film forming polymers.23 These polymers should form a clear flexible film at skin temperature.24 The list of polymers along with their molecular weight and properties are mentioned in Table 3
Film Forming Polymers
Table no.3
|
Polymers |
Properties |
|
Hydroxypropyl
|
|
|
Ethyl cellulose (EC) |
|
|
Chitosan |
|
|
Eudragit (polymethacrylates copolymer) |
|
|
Hydroxypropyl cellulose |
|
|
Polyvinyl alcohol (PVA) |
|
|
Silicones Polydimethylsiloxane (PDMS) |
|
|
Acrylates copolymer Avalure® AC 118, AC 120 |
|
Solvents
Solvents are an important component in film formation. The solvents used in film-forming systems contribute to the solubilization of the drugs and have an influence on the permeation of the drugs. The commonly used solvents for topical and transdermal application 31 are listed in Table 4. As these solvents are widely used, their safety for long-term use has been demonstrated.
Solvents Used in Topical Systems
Table no. 4
|
Category |
Examples |
|
Glycols |
Propylene glycols, polyethylene glycols |
|
Alcohols |
Ethanol, butanol, isopropanol, benzyl alcohol, lanolin alcohols, fatty alcohols |
|
Other solvents |
Ethyl acetate, oleic acid, isopropyl myristate |
Plasticizers
Plasticizers are used in the film forming systems to impart flexibility to the film and improve the tensile strength of the film formed. The plasticizer used should be compatible with the polymers used and should have low skin permeability. Commonly used plasticizers are Glycerine, polyethylene glycol, sorbitol, dibutyl phthalate, propylene glycol, triethyl citrate etc. 32
Evaluation of Film Forming System
Film Formation
The films are formed in a Petri dish or on an excised pig ear skin. Film-formation is evaluated and rated as complete and uniform, incomplete or non-uniform, with or without precipitation of the film-forming polymer. The cosmetic aspects of the film are given in terms of transparency or opaque, sticky or dry, peelable or non-peelable 33.
Film Flexibility
Film flexibility is evaluated on the basis of cracking and skin fixation and this is determined by stretching the skin in 2–3 directions. The film is rated flexible if there is no cracking or skin fixation and non-flexible if there is cracking and skin fixation.
Drying Time
The time taken by the polymeric solution to dry on a glass slide or the hand arm is referred to as drying time. The drying time was recorded by using a digital stopwatch. After a fixed time period a glass slide is placed on the film without pressure. If no liquid is visible on the glass slide after removal, the film is considered dry 34. If remains of the liquid are visible on the glass slide the experiment is repeated with an increase in drying time. A good FFS should have a minimum drying time to avoid long waiting time for the patient.
Stickiness
The stickiness of the film formed is determined by pressing cotton wool on the dry film with low pressure. Depending on the quantity of cotton fibres that are retained by the film, the stickiness is rated high if there is dense accumulation of fibers on the film, medium if there is a thin fiber layer on the film and low if there is an occasional or no adherence of fibers. This evaluation parameter is essential, as the formulation should be non-sticky to avoid adherence to the patients' clothes.35
In Vitro Diffusion Study
The in vitro diffusion studies are used to predict the permeation properties of drugs in vivo. The Franz diffusion cell is used to determine the release profile of the drug from the film-forming system. The cell consists of two compartments, the donor and the recipient compartment, between which the diffusion membrane is attached (egg membrane or cellophane). The donor compartment is exposed to the atmosphere, while the receptor compartment contains the diffusion medium. The sampling arm in the receptor compartment allows the sample to be taken. A predetermined amount of the drug-containing film-forming formulation is applied to the donor compartment. Samples are taken and analyzed for drug release using a suitable spectroscopic method.38
CONCLUSION
The film-forming system provides a novel platform to deliver drugs both topically and transdermally to the skin. These film-forming systems are simple and offer the advantages of transparency, non-greasiness, reduced skin irritation, wipe-off resistance, longer dwell time, greater dosing flexibility, improved patient compliance and aesthetic appearance. Although much work has been done on these systems, little data is available on their delivery efficiency. As a result, there are few marketed products. Further research is needed to prove the relevance of the film-forming system as a transdermal delivery system, but the results obtained are encouraging for the further development of this novel technology for topical drug delivery.
REFERENCES
Dipali Rathod, Anushka Deshmukh, Dr. Arun Mahale, Film-Forming Sprays for Topical Drug Delivery: A Review of Current Developments and Future Perspectives, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 7, 1154-1163. https://doi.org/10.5281/zenodo.15844669
10.5281/zenodo.15844669
