Orally Dissolving Strips: A Novel Formulation for Quick Drug Absorption

The oral route is the most preferred and convenient method of drug administration due to its cost-effectiveness, ease of use, and high patient compliance. However, conventional oral dosage forms like tablets and capsules present challenges for specific populations, including pediatric, geriatric, and bedridden patients, as well as individuals with dysphagia or fear of choking. To address these issues, innovative drug delivery systems such as orally dissolving strips (ODS) have been developed, offering rapid disintegration in the mouth without the need for water. Orally dissolving strips are thin, flexible films that incorporate active pharmaceutical ingredients (APIs) along with excipients like film-forming agents, plasticizers, and flavoring agents. Upon placement on the tongue, they dissolve quickly, allowing for rapid drug release and absorption through the oral mucosa, thereby offering a faster onset of action compared to traditional tablets. This drug delivery system enhances patient compliance, especially in emergency situations, during travel, or for individuals with limited access to water. Paracetamol, commonly referred to as acetaminophen, is a widely utilized medication known for its effectiveness in relieving mild to moderate pain and reducing fever. Despite its extensive use in tablet, capsule, and liquid forms, these traditional formulations may not be suitable for all patients, particularly children and the elderly. To overcome these limitations, we have developed paracetamol orally dissolving strips using hydroxypropyl methylcellulose (HPMC) as the primary film-forming polymer due to its excellent film-forming properties, safety, and compatibility with various pharmaceutical excipients. The objective of this research is to optimize the formulation of paracetamol ODS by evaluating the physicochemical properties, mechanical strength, disintegration time, and drug release profile.

The Study Involves the Preparation of Four Formulations:

Table 1: Ingredients Used in the Development of Paracetamol ODS Formulation

2. Formulation 2: Excipients with paracetamol to assess drug loading and distribution.

3. Formulation 3: Trial formulation with super disintegrant (Xanthan gum) for rapid disintegration evaluation

4. Formulation: Final optimized formulation containing excipients, paracetamol, and a coloring agent to enhance aesthetic appeal.

These fast-dissolving strips aim to improve patient compliance, provide rapid relief from pain and fever, and serve as an effective alternative to conventional oral dosage forms.

Key Features of Fast Dissolving Films (FDFS)

• Easy to administer
• Eliminates choking risk
• Avoid First-pass metabolism
• Accurate dosing
• Ideal for acute condition
• Lower dosage requirement
• No-invasive alternative

Advantages of Fast Dissolving Films (AFDF)

• Easy to take
• No water needed
• Better taste
• Longer shelf life
• Improves patient compliance
• Faster action with less liver impact
• Local effect in the mouth
• Quick dissolving

Disadvantages Of Fast Dissolving Films (DFDF)

• Limited drug dose (1–30 mg only)
• Difficulty incorporating high drug doses
• Fragile and prone to tearing
• Sensitive to moisture and humidity
• Expensive manufacturing process

Types of Orally Dissolving Strips (TODS)

For ease of understanding, fast dissolving technologies can be categorized into three major groups:

1. Lyophilized Systems

2. Compressed Tablet-Based Systems

3. Oral Thin Films (OTFs)

1. Lyophilized Systems

• Lyophilized systems are the most commercially successful due to their high sales volume and global approvals. This technology involves preparing a suspension or solution of the drug with structural excipients, which is then molded into tablet-like units using blisters or molds. The units are frozen and subjected to lyophilization (freeze-drying), creating highly porous structures. This porosity enables quick saliva or water penetration, leading to rapid disintegration.
• The drug loading capacity in these systems varies based on the solubility of the active pharmaceutical ingredient (API). While lyophilized systems may have a slightly lower dose capacity compared to tablet-based systems, they offer faster disintegration and the ability to incorporate taste-masking agents effectively.

2. Compressed Tablet-Based Systems

• Compressed tablets are manufactured using conventional tableting techniques, primarily through direct compression. The disintegration speed of these tablets is enhanced by incorporating water-soluble excipients, super disintegrants, or effervescent agents, which facilitate rapid moisture penetration.
• The hardness and friability of the tablets depend on the formulation and compression process, affecting their disintegration rate and packaging requirements. Some tablets require specialized packaging (e.g., CIMA Labs' PackSolv) to maintain product integrity.
• An advanced example includes Biovail’s Fuisz Technology, which uses the Shearform process to create drug-loaded candy floss-like structures for tableting. While compressed tablets can accommodate higher drug doses and taste-masked particles, their disintegration time is generally slower compared to lyophilized systems and thin films.

3. Oral Thin Films (OTFs)

• Oral Thin Films (OTFs), also known as oral wafers, are flat, flexible films designed for administration in the oral cavity. Although this technology has been around for some time, it has gained significant attention in recent years for fast-dissolving drug delivery.
• Initially popular in the confectionery and oral care industries (e.g., breath freshening strips), OTF technology has evolved for pharmaceutical applications, including vitamins, OTC medications, and prescription drugs. Companies experienced in transdermal drug delivery have adapted their polymer coating technologies to develop OTFs. These films dissolve quickly upon contact with saliva, offering rapid onset of action, improved patient compliance, and ease of administration without the need for water.

Formulation Methods of Orally Dissolving Strips (ODS)

The preparation of orally dissolving strips involves various conventional and advanced techniques, each offering specific advantages depending on the          desired film characteristics. The following methods are commonly employed for the formulation of ODS:

1.  Solvent Casting Method (Method Used in This Study)

In this research, paracetamol ODS were prepared using a modified two-phase solvent casting method, designed to enhance drug dispersion and film uniformity. The process involved two separate phases:

Phase 1: Hydroxypropyl methylcellulose (HPMC) was dissolved in 10 ml of distilled water under continuous mechanical stirring to form a viscous polymeric solution.

Phase 2: Paracetamol was dissolved in another 10 ml of distilled water with the addition of ethanol, using a hot plate to ensure complete dissolution. After preparing both solutions, they were combined with plasticizers (glycerin), sweeteners, amaranth coloring agent, and menthol oil to improve the film’s organoleptic properties. The final mixture was cast onto an oil-coated petri dish to prevent sticking and was dried in a hot air oven at 50–55°C. Once dried, the films were carefully peeled off and cut into uniform strips. This method offers enhanced drug distribution, better control over film thickness, and improved mechanical properties of the strips.

Figure 1: Solvent Casting Method for Paracetamol

This is one of the most widely used techniques for ODS preparation. In this method, the film-forming polymer is dissolved in a suitable solvent, typically water or alcohol. The drug is either dissolved or uniformly dispersed in the polymeric solution along with plasticizers, sweeteners, colorants, and flavoring agents. The resulting mixture is cast onto a flat surface to form a uniform layer, dried under controlled temperature conditions, and then peeled and cut into desired sizes.

Figure2. Industrial Setup for Solvent Casting Method in ODS Preparation

Hot-melt extrusion is a solvent-free process, ideal for drugs that are stable at high temperatures. The drug, polymer, and excipients are blended and introduced into an extruder where they are melted and mixed to form a homogeneous mass. This mass is then extruded through a flat die to create thin films. After cooling, the films are collected and cut. This method provides uniform drug distribution and enhances the bioavailability of poorly soluble drugs.

Figure 3: Schematic Representation of the Hot-Melt Extrusion Process

In this technique, the drug is dispersed within a polymer matrix to form a solid dispersion, enhancing solubility and dissolution rates. The drug-polymer mixture is melted, homogenized, and extruded to form thin films. Solid dispersion extrusion is particularly effective for improving the bioavailability of poorly water-soluble drugs.

Figure 4: Schematic Representation of the Solid Dispersion Extrusion Process

This method involves the preparation of a semi-solid gel by dissolving the polymer and drug in a suitable solvent, often with the addition of plasticizers. The semi-solid mass is then cast onto a flat surface to form a film of uniform thickness. After drying, the film is peeled off and cut into strips. This method allows precise control over drug content and film properties.

6. Rolling Method

In the rolling method, the polymer-drug solution or suspension is continuously fed between rollers to form thin films. The film passes through heated rollers to facilitate solvent evaporation, ensuring uniform thickness and consistency. This technique is stable for large-scale production due to its continuous nature and high throughput.

Figure 5: Schematic Representation of the Rolling Method

Several advanced techniques are being explored to optimize ODS characteristics:

Electrospinning Method: Utilizes an electric field to create nanofibrous films with high surface area, promoting rapid dissolution. Lyophilization (Freeze-Drying) Method: Involves freezing the polymer-drug solution and sublimating the solvent under vacuum, resulting in porous films with fast disintegration. 3D Printing Technology: Allows precise control over film composition, drug loading, and release profiles, offering potential for personalized medicine. Development of Paracetamol Orally Dissolving Strips: Ingredients and Preparation Method (Research Work on ODS)  In this study, we formulated orally dissolving strips (ODS) of paracetamol using a stepwise approach. The development was carried out in four stages, each focusing on the gradual addition of key components:

Formulation 1: Base Film (Only Excipients, No Drug, No Color)

Ingredients Used:

• HPMC (Film-forming agent)

• Glycerin (Plasticizer for flexibility)

• Sucrose (For taste)

• Methyl paraben
• Ascorbic acid

• Distilled water (Solvent)

Table 2: Stepwise Preparation of Base Film (Only Excipients, No Drug, No Color)

Figure 6: Visual Comparison of Orally Dissolving Strips Showing Progressive Formulation Stages – Basic Transparent Strips, Drug-Loaded White Strips, lower white xanthin gum containing strips and Optimized Pink Strips with Enhanced Aesthetic Appeal.

Table 7: Composition of paracetamol orally dissolving strips (ODS) with ingredients, quantities, and their functions

The oral strips were prepared using the solvent casting method. The procedure involved the following steps:

1. Preparation of Drug Solution:

Paracetamol was dissolved in ethanol to enhance its solubility. The drug solution was then added to the pre-prepared HPMC solution under continuous stirring then into excipients solution and stirrer continuous.

Figure 7: Preparation of Paracetamol and HPMC Solution Using Magnetic Stirring

The excipient solution was prepared by dissolving glycerin, ascorbic acid, methyl paraben, sucrose, peppermint oil, and Amaranth coloring agent in a suitable solvent. The drug solution was then added to this excipient mixture, and both solutions were mixed thoroughly using a mechanical stirrer to ensure uniform distribution.

Figure 8: Homogeneous drug-excipient solution for orally  dissolving strips

The prepared homogeneous solution was poured into Petri dishes and evenly spread to form a thin layer. The solution was dried at 50°C in a hot air oven to form solid strips.