Film-Forming Gels: An Innovative Drug Delivery System for Enhanced Therapeutic Efficacy

Neethu K. C., Mounika R., Muralidharan C., N. Jeevitha, N. Nandhishri, Namitha,

doi:10.5281/zenodo.16811197

Review Paper | Open Access
Volume 03 | Issue 08 | Article Id IJPS/250308109

Film-Forming Gels: An Innovative Drug Delivery System for Enhanced Therapeutic Efficacy
Neethu K. C.* Mounika R. Muralidharan C. N. Jeevitha N. Nandhishri Namitha
Department pf Pharmaceutics, The Oxford College of Pharmacy, Hongasandra, Bommanahalli Bengaluru.

Abstract

Film forming gels have emerged as an innovative and novel drug delivery system that offers controlled and prolonged drug release. These formulations form thin, flexible and transparent film upon application and allow for better drug interpretation and bioactivity while maintaining patient comfort and convenience. These are formulated to overcome the drawbacks of conventional dosage forms like topical and transdermal drug delivery systems. The topical film forming gel formulation comprised of polymers, solvents, drug and plasticizers and each component plays a critical role in therapeutic action. The specialized mechanism of film forming gel involves solvent evaporation that leads to super saturation. It shows better drug permeation through the skin by raising supersaturation state of film forming gel. Key advantages over conventional dosage form includes improved bioavailability, localized therapeutic action, ease of use, enhanced stability, prolonged storage time, less frequent administration and aesthetic acceptability. This review provides comprehensive insight into the composition, mechanism of action, formulation, evaluation parameters and diverse pharmaceutical application.

Keywords

Film forming gels, polymers, plasticizers, Transdermal drug delivery system

Introduction

Even though the peroral route is the highly patient compliant and commonly favored route for drug delivery, it shows low bioavailability. It is mostly due to enzyme catalyzed degradation in gastrointestinal tract and poor permeability of drug into target treatment site^(1,2). Transdermal dosage form administration system is the ideal form of drug administration because of noticeable advantages over other routes of administration. Transdermal delivery offers convenient, pain free self-directive administration for patients. Through this route delivery of fast acting drugs is easy and reduces dosing frequency and peak plasma concentration and fluctuation in drug concentration due to conventional dosing⁽³⁾. To get therapeutic effects of drugs in TDDS it is necessary to study permeation characteristics of drugs into or through the skin⁽⁴⁾. A novel approach called Film forming gel is an exceptional choice over conventional and other transdermal formulations. Film forming gels are non-solid dosage forms which form thin film on topical application. These gels primarily contain evaporative solvents, polymers, plasticizers and active ingredients⁽⁵⁾. On skin contact, leaving behind a residual thin film forming excipients and drug upon volatilization of solvent allowing them to aid sustained and prolonged drug release topically⁽⁶⁾. The adherent film must not wash off or rub off from the skin and function as a barrier. The active film needs to form a uniform carrier system for active pharmaceutical ingredients on the skin with enhanced persistence, by which active ingredients readily absorb into the stratum corneum⁽⁷⁾. These films lessen the risk of removal due to clothing friction and movement of the body. They also offer a set of advantages including betterment of drug delivery, uniform spreading over wide areas and convenient unit dosing ⁽⁸⁾. Transparent and colourless nature of the gel makes it aesthetically pleasing. Gel shows good protection to the wound from external agents and good adherence to the skin⁽⁷⁾. These films help in two ways, preventing bacterial infection risk and facilitate the permeation of oxygen and carbon dioxide⁽⁹⁾. Film forming gel is having high efficiency in release and excellent permeability, in addition to being non-greasy, uniformly spreadable, easy to wash off and strain-resistant⁽¹⁰⁾.

Advantages Over Conventional Dosage Forms^{(4,10,11,12,13)}:

Drugs incorporated in film forming gels shows better bioavailability due to enhanced absorption through the skin or mucous membrane.

These provide rapid therapeutic response than the other traditional dosage forms like tablets, capsules, solution, emulsion, and suspension.
Film forming gels have optimal release profile along with high absorbency due to its dual-action release i.e., film and gel
The probable benefits include elusion of first-pass clearance by the liver, better patient adherence, wound repairing, and convenient use on the skin.
These have the ability to produce long-term drug release for about 12 hours into skin and on the site of application.
It is non-greasy in nature, odorless and provides a pleasant feel when applied on the skin as compared to creams and ointments.
Film forming gels cling to the affected area for a long period of time and facilitate controlled drug release so that frequent dosing is does not be done.
Considering their formulation characteristics, gels tend to show longer shelf stability while compared to other conventional dosage forms as they are prone to degradation.

Mode of Action of Film-Forming Gels:

Film-forming gels are topically applied to the skin, where they form a thin and clear film by solvent volatilization. After the application of product on the skin, the composition of the film-forming gels changes due to the loss of the volatile components in the vehicle which leaving the residual film on the skin surface. So, the concentration of the product increases by reaching the saturation level or even super saturation level on the skin surface. By increasing the thermodynamic activity of the film-forming gel, super saturation shows the enhanced drug flux through the skin without affecting the skin barrier, hence by reducing the side effects or irritation⁽¹⁴⁾.

Super saturation concept can be described using a modified form of Fick’s law of diffusion, as presented in equation-1:

J = DKCv/h [1]

Where,

J = drug permeation rate [flux]

D = drug diffusivity coefficient

Cv = concentration of the drug

h = barrier thickness

According to this equation, the drug’s concentration and rate at which it permeates through the skin are proportionate. However, this happens when all the drugs are dissolved in the vehicle.

Eq-2 shows the modified form of Fick’s law of diffusion:

J = aD/ γh [2]

Where,

a = thermodynamic activity of drug within the formulation

γ = thermodynamic activity of drug within the membrane barrier

As per the equation shown above, the flux of the drug and thermodynamic activity of the membrane are directly proportional to each other, this relates to the saturation. Hence it shows increase in the super saturation levels and thermodynamic instability.

Fig 1: Mode of action of film forming gels

Composition And Function of Film Forming Components:

Film forming gel should contain volatile vehicle, film forming polymer, active ingredient and plasticizer, penetration enhancer to achieve the desired therapeutic effect.

1.Drug:

For effective use in a transdermal film forming system, the drug should possess characteristic physicochemical properties that are independent of the delivery system. Whether the drug is intended for cutaneous or percutaneous application, it must be capable of permeating through the stratum corneum. The drugs used for these film forming gels are biologically potent, rapidly penetrate into the skin, non-irritating to the skin, stable to the epidermal enzyme. Due to the hydrophobic nature of the stratum corneum, lipophilic drugs penetrate the skin better than hydrophilic drugs. The partition coefficient (log P) influences transdermal absorption pathway of drug and it usually falls within the range of 1 to 3. The molar mass shows an important function here, low molecular weight molecules undergo more rapid diffusion across the skin than larger molecules and ideally it should be below 500 Da^(7,12).

2. Polymer:

Polymers are often incorporated individually or combined with other film forming polymers to form optimal film qualities⁽¹²⁾. The polymer incorporated should be free from leachable impurities, non-toxic and non-irritant. Water-soluble polymers serve as a film forming agent to produce thin film with fast disintegration and strong mechanical strength⁽¹⁵⁾. Sustained drug release, increased systemic availability and minimum side effects can be achieved by using polymers in such way that,

1.Smaller the size of polymer particles, optimum drug release into the site of action.

2. Aggregated polymeric drugs offer controlled drug release, mitigate the risk of overdose and adverse effects.

3. Biodegradable polymers can be metabolized and eliminated naturally⁽¹⁶⁾.

Smaller polymers with low molecular weight are usually used for film forming gels. Polymers with high molecular weight increase the viscosity of the formulation during solvent volatilization. Moreover, smaller, short-chained polymers align more efficiently in space, achieving interchain spacing for gelation. Once the low boiling solvent evaporates, the film spreads uniformly across the skin, minimizing the thickness variation⁽⁷⁾. Table 1 presents polymers with diverse properties used for formulating the film-forming system.

Table 1: Polymers used in film forming gel ^{(12,17,18,19,20)}

Polymer	Properties
Chitosan	Controls drug release High quality film formation Enhances drug permeability and penetration through the cell junction and mucosal membrane
Hydroxypropyl Methylcellulose (HPMC)	Form a light, non-oily, uniform film with good consistency Chemically inert with other constituents Easy dispersion and lubrication
Ethyl cellulose	Non-irritant, non-toxic and non-allergenic Forms stronger film
Methyl cellulose	Water-soluble
Hydroxypropyl cellulose	Non-ionic, pH independent polymer with water solubility
Polyvinyl alcohol	Biocompatible and good film forming and adhesive property
Polyvinyl pyrrolidone	Absorption enhancer Soluble in water and other solvents Adhering and holding capacity
Eudragit	Clear, flexible and self-adhesive
Acrylates copolymer	Strong, ventilated and abrasion resistant film
Silicones Polydimethylsiloxane (PDMS)	Moisture permeable film Provide sufficient substantivity and durability
Carbopol (Polyacrylate)	Water soluble, pH dependent
Crosslinked polymer layer XPL	Retains elasticity and adhesive
Dermacryl 79 (Carboxylates acryl polymer)	Hydrophobic
Macrogol	Hydrophobic
Poloxamer (Polyethylene polypropylene glycol)	Temperature sensitive
Plastoid	Water-insoluble
Quaternary polymethacrylate	Water-insoluble
Sepineo P600	Water-insoluble

3. Solvents:

In the film forming system solvent is one of the important compounds despite not becoming the part of the film formulation on the skin as a result of its quick evaporation. It is necessary for the chosen solvent to exhibit adequate skin compatibility, even in case of barrier disturbance or skin injury. On evaporation it should not irritate the skin. The selected solvent must offer solubility for the polymer as well as for the drug. The solvent with high solubilizing capacity for the drug provides considerable change in drug loading, thereby regulating the drug delivery to the skin. The solvent can also modulate the rate of drug diffusion. Based on solvent profile and its ability to enhance penetrate, despite short skin contact time it can aid in drug delivery to different level^(7,12,14).

Solvents used in film forming gels:

Category	Example
Alcohols	Short chain alcohol (Ethanol, butanol, isopropanol), aromatic alcohol (benzyl alcohol) and higher alcohol such as lanolin alcohols and fatty alcohols
Glycols	Polyethylene glycols, propylene glycols
Other solvents	Isopropyl myristate, ethyl acetate, oleic acid, water

Plasticizer:

One of the major problems in formulation of film forming systems is that many polymer films are brittle and too hard. If the film is too stiff, it cannot move with skin, in particular around elbows. Skin adhesion also reduced. This issue can be overcome by mixing different polymers in one formulation and by combining their good qualities, however the use of plasticizer is required⁽⁷⁾. Plasticizers are incorporated into the film forming system to provide pliability and improve the film’s mechanical strength. The chosen plasticizer must be compatible with employed polymers and allow only minimal skin permeation⁽¹²⁾.

Plasticizer utilized in film forming gels^(7,21)

Plasticizer	Polymer	Concentration (%)
Triacetin	Eudragit E 100, Eudragit NE 40D, Acrylate copolymer	1.43-5.48
Sorbitol	Polyvinyl alcohol, Chitosan	2-20
Dibutyl phthalate	Cellulose acetate, Ethyl celluloses, Hydroxypropyl methyl cellulose, Polyvinyl pyrrolidone	10-40
Propylene glycol	Cellulose acetate, pectin, Polyvinyl alcohol, Polyvinyl pyrrolidone, Ethyl cellulose, Hydroxypropyl methyl cellulose, Carboxymethyl cellulose	5-50
Polyethylene glycol 400, 600 and 3350	Carboxymethyl Guar, Cellulose acetate, Polyvinyl alcohol, Polyvinyl pyrrolidone, Eudragit E 100, Carbopol, Hydroxypropyl cellulose, Polycarbophil	5
Triethyl citrate	Eudragit E 100, Hydroxypropyl cellulose, Silicon gum, Polyvinyl alcohol, Polyisobutylene	6
Glycerin	Polyvinyl alcohol, Polyvinyl pyrrolidone	4-50
Tributyl citrate	Eudragit NE 40D	25-125
Polysorbate 80	Cellulose acetate	25-50

Method Of Preparation of Film Forming Gel^(5,10,13):

1.Preparation of polymeric solution:

Accurately weigh the specified amounts of film-forming polymer as per formulation and dissolve it in suitable solvents under constant stirring until a clear and homogenous polymeric solution is formed.

2.Drug solution preparation:

Specified amount of drug is dissolved in suitable solvent depending on its solubility. Stir constantly until completely dissolved.

3.Both the polymeric solution and drug solution were added, adding necessary excipients like plasticizer and mixing continuously to get homogenous gel.

4.Prepared film-forming gel was placed in an airtight container and kept at room temperature until required.

General Evaluation Parameters of Film-Forming Gels:

1.Physical appearance:

The physical appearance of film forming gels was evaluated to ensure the color, transparency and texture of the formulation^(13,23).

2. pH:

Film forming gels pH were assessed using high precision calibrated digital pH meters. A 1:100 ratio of gel to distilled water was prepared, allowing it to stabilize for 120 minutes. For accuracy, triplicate pH readings were taken for each formulation, and the average value was computed. ⁽¹³⁾.

3.Film Thickness:

The dimensional thickness of film forming gels was precisely measured using vernier calipers with high accuracy. The gels were transformed into circular film samples and the thickness was recorded at five distinct points on each sample, then the average value was computed accurately.⁽¹³⁾.

4.Film weight:

Accurate amount (1 gram) of film forming gel was dispensed onto a Petri dish and left to air dry completely overnight. Upon drying, the exact weight of the film was recorded using a highly sensitive digital electronic balance⁽²⁴⁾.

5. Weight variation test:

Three circular film samples of diameter 2 cm were prepared for each formulation. Weight of each film was recorded and average weight was calculated⁽¹³⁾.

6.Phase transition time:

Phase transition time refers to time required for the gel to transform into a film. One gram portion of gel preparation was gently poured on a petri plate, allowing slightly spreading, then kept on a thermally regulated plate maintained at 37°C. The exact elapsed time span for the complete conversion from gel state to solid film state was precisely recorded⁽²⁵⁾.

7.Spreadability:

Spreadability was determined by using glass slides. The gel was then embedded between both the glass slides. 1 kg weight of about 1 kg was applied over the top of the slide until the spreading stop and the spreading time was noted down. The gel overflowing at the edges was removed. The distance travelled by the gel on the glass slide was measured. The subsequent formula was used to compute the spreadability⁽²⁵⁾:

S=M×L/T

Where, S=Spreadability of the gel

M=Mass of the gel or quantity taken

L=Distance travelled by the glass slides

T=Time required for the slides to fully spread against each other (in sec)

8.Extrudability:

To analyze the force required to discharge the gel from a container, an extrudability test is one of the useful methods. collapsible metal tubes with a nasal tip of 5mm opening tube were filled with gels. By quantifying the amount of gel extruded through the tip when pressure was applied to the tube, extrudability was determined⁽²⁶⁾.

9.Drying time:

For evaluating the dosage form’s drying period, a volunteer was selected who enrolled in the study with informed consent. The formulation was spread on the inner region of the participant’s forearm. After two minutes the glass slides were laid on the film with no applied pressure. If no evident liquid remnant was detected on the glass slide after being taken off, the film was deemed to be dried out. If any fluid remnant was detected over the glass slide, then the test was redone until dryness of the film was confirmed. The reduced drying time would enhance patient adherence due to lesser waiting time for film generation^(5,25).

10.Folding endurance:

Folding endurance was measured by using a thin segment strip of film having the dimensions of 2cm×2cm was folded repeatedly in the same area until breakage happened. Folding endurance denotes the total number of folds a film can tolerate at the same point without structural failure⁽¹³⁾.

11.Viscosity Measurement:

Brookfield digital viscometer-DV II RVTDV-II USA was used to determine the viscosity of the film-forming gel. The gel formulation was kept in a sample holder of the instrument and let settle for 5min. The spindle (TF 96) was rotated at 50 rpm with temperature stabilized at 25°C, to measure the viscosity⁽⁴⁾.

12.Water vapour permeability:

The water vapour permeability (WVP) was analyzed in accordance with method adapted from the British Pharmacopoeia. Circular films of 2cm diameter were cut from the dry film sheet with the help of a scalpel. During sample preparation 10mL of glass vials) opening diameter=1.2cm; Area-1.13cm²) were filled with 8g of distilled water, covered with the formed circular film and tied using elastic bands. The glass vials were covered with the circular film specimens and sealed with aluminum foil. The experiment began by uncapping the vial and original weight was taken. It was subsequently stored in a desiccator containing a desiccant to create low relative humidity environment. The temperature was maintained at 37°C for 72 hours, the sample was reweighed and the loss of weight can be determined by using the below formula⁽⁵⁾:

WVP=W/ (A×t) (g.cm^-2 24 hours)

Application^(12,27,28):

It can be used as a translucent sheet mask for skin nourishment and breakouts. The film forming gels in the cosmetic formulations are used in the development of sunscreens, moisturizers, and anti-aging agents in order to improve the skin texture and to retain a long-lasting effect on skin. It acts as a base for membrane barrier used in the industry. Barrier membranes are broadly used to safeguard labors from cleansers, chemical reactants, other toxic substance, heat radiation, UV light exposure etc.

Ex: Hydrophilic and hydrophobic gels and creams, sunscreen gels. They also have the capacity to withstand in some stereotypical inflammatory skin condition like psoriasis, eczema and acne. These film-forming gels create a protective film on the surface of the wounds, ensuring to remain moist to facilitate wound healing.

CONCLUSION:

Film forming gels offer a promising and novel advancement in topical and transdermal drug delivery systems by providing controlled, prolonged release, enhanced patient adherence, improved bioavailability and ease of application. Their ability to form thin, flexible, transparent film ensures effective drug permeation, stability, aesthetic acceptability and comfort. Polymers, solvents, and plasticizers can be carefully formulated to optimize these systems for a diverse range of therapeutic and cosmetic applications. Ongoing research and developed in this area will further expand their application, ensuring.

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