Development of Starch-based Orodispersible Films for Paracetamol Delivery: A Comparative Study

Abstract

Orodispersible films (ODFs) have emerged as practical dosage forms due to their ease of application, dosage flexibility, and rapid disintegration in the oral mucosa without water, enabling rapid drug release. Analgesics and antipyretics are expected to have rapid effects, particularly in pediatric patients. In this study, ODFs were produced using a simple method that provides rapid drug release and doesn’t require additional components like cross-linking agents. The aim of the study was to develop paracetamol-loaded starch-based films useful for children, patients experiencing vomiting, or those having difficulties. Orodispersible films were prepared via the solvent casting method using wheat, rice, and corn starches. The films were evaluated for their physical properties, including thickness, mass, surface pH values, swelling index, and disintegration and dissolution time. The results revealed that all films exhibited dissolution times of under 3 min, with approximately 80% of paracetamol release, demonstrating rapid and efficient drug delivery. The surface pH values were close to the pH of the oral cavity, indicating minimal risk for irritation. The characterizations of films were determined using Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) techniques. FTIR-ATR analysis showed no differences between starch types and paracetamol was physically bound to the films. XRD patterns indicated amorphous structures resulting from starch gelatinization. TGA analysis showed rice starch films exhibited the highest weight loss and the least thermal stability. The results demonstrated synthesized ODFs can be utilized as carriers for paracetamol and could potentially be used for other active ingredients.

Introduction

Orodispersible films (ODFs) have gained significant attention in recent years as an innovative and patient-friendly dosage form. Traditional dosage forms may not be suitable for certain patient groups, including pediatrics, geriatrics, and individuals with dysphagia or psychiatric conditions. Some individuals may struggle to take their prescribed doses due to difficulties in swallowing, while others might keep tablets under their tongues and take them off later [1]. In some cases, medicinal products containing the required dosage may not be available, and practices such as splitting tablets and opening capsules can lead to inaccurate doses and other consequences for patient safety and treatment efficacy [2]. Incorrect dosage of medication can cause serious health problems, especially in pediatric patients; for example, pediatric patients require medication dosages appropriate for their ever-increasing body weight [3]. At the same time, the method of administration and the amount of medication are also very important for the effectiveness of the medication [4, 5].

ODFs are polymeric matrices that have been developed to avoid difficulties and challenges such as swallowing or removing from the mouth, meeting many requirements for effective drug delivery platforms [2, 6]. ODFs offer certain advantages, including more effective patient compliance, dosage flexibility, and ease of application. The mucoadhesive properties of the films reduce the risk of accidental or intentional removal of medication from the mouth. Due to their mucoadhesive properties, ODFs are particularly beneficial for bedridden patients, those with Parkinson’s disease, those suffering from mucositis, nausea, and vomiting, and those with difficulty swallowing [7, 8].

ODFs are generally composed of water-soluble polymers and can be single- or multilayer systems intended to rapidly disintegrate in the mouth before being swallowed. Their formulations typically consist of one or more polymers containing an active pharmaceutical ingredient (API), film-forming polymers, plasticizers, sweeteners, flavorings, and colorants [8, 9]. These films can be tailored by their composition and properties, such as disintegration rate, drug loading capacity, and mechanical properties. Film properties can also be modified by varying the type, amount, or grade of polymers used in film production or by varying the manufacturing conditions [10].

Polymers produced directly from biological sources or synthesized from biological building blocks are classified as biodegradable biopolymers. Biopolymers offer significant advantages in drug delivery due to their drug loading and release properties. Numerous natural, semi-natural, and synthetic polymers have been investigated for use in ODFs formulations. Natural polymers are gaining increasing interest in the pharmaceutical industry, particularly due to their safety, biocompatibility, and biodegradability [11, 12]. Starch, a natural polymer belonging to the polysaccharide group, is found abundantly in nature [11]. Starch-based biodegradable materials have gained popularity due to their affordability and low cost, non-toxicity, and widespread availability [13, 14].

Starch is widely used in many industries as an environmentally friendly material due to its biodegradability and consists of two structurally distinct α-D-glucan components: linear amylose and highly branched amylopectin [15]. Starches originated from different botanical sources have the same structural units but differ in their molecular structures and the ratio of amylose to amylopectin, which in turn affects their physical and chemical properties [15–17]. The differences in their molecular structures and interactions significantly affect the properties of the films [18]. Native starch possesses difficulties in film formation because of its non-thermoplastic nature and tends to be brittle due to strong inter- and intramolecular hydrogen bonds; however, it can be gelatinized with water and other plasticizers such as glycerol to produce a thermoplastic starch film [15, 17, 19]. Plasticizers can penetrate the starch matrix, break down intramolecular and intermolecular hydrogen bonds, and reduce molecular interactions to increase the flexibility and processability of films because of their low molecular weight and high boiling point [20]. Volatile plasticizers such as water and non-volatile plasticizers such as glycerol or sorbitol are commonly used to provide elasticity and prevent brittleness of starch-based films [19].

The most common method for producing ODFs is solvent casting, which involves dissolving or dispersing polymers, active ingredients, and additives in a suitable solvent. The resulting homogeneous viscous solution is then poured into molds and allowed to dry [21, 22]. Furthermore, the solvent casting technique makes it easier to customize dosage because films can be formed in small quantities and readily divided into smaller pieces to satisfy precise dosage requirements [21].

Paracetamol, also known as acetaminophen, is one of the most widely recognized analgesics and is often used as a first-line treatment for many chronic pain conditions. It is generally primarily a fever reducer and pain reliever, and it is considered safe for children and pregnant women when taken at prescribed doses. Paracetamol does not possess the same anti-inflammatory properties as aspirin or ibuprofen; it is an effective alternative for patients who are sensitive to aspirin [23, 24]. Paracetamol is commonly used to relieve toothache, migraine, acute back pain, and pain following surgery [25].

According to the European Medicines Agency and Supplement I Japanese Pharmacopoeia 17th Edition (Supplement I to JP17), ODFs are thin, non-sticky dosage forms designed to dissolve rapidly in the oral cavity. They have attracted considerable attention due to their promising applications as flexible and age-appropriate drug delivery systems, particularly suitable for pediatric patients [26, 27].

There is a significant need to develop drug delivery platforms that meet the needs of the specific patient groups and address swallowing difficulties. Analgesics and antipyretics are expected to be quickly effective, especially in pediatric patients. In this context, this study developed biocompatible films that rapidly disintegrate in the oral cavity. The films were loaded with paracetamol, and their release rates were investigated. Unlike many previous studies, the films in this study were produced using a simplified method and formulation without crosslinking agents or additional excipients.

Download the full article as PDF here Development of Starch-based Orodispersible Films for Paracetamol Delivery

or continue reading here

Arioz, E., Ogunc, M. “Development of Starch-based Orodispersible Films for Paracetamol Delivery: A Comparative Study”, Periodica Polytechnica Chemical Engineering, 2025. https://doi.org/10.3311/PPch.42034

Read more articles on Orodispersible Films here:

• Hydroxypropyl Methylcellulose—A Key Excipient in Pharmaceutical Drug Delivery Systems
• Orodispersible films prepared by hot-melt extrusion versus solvent casting
• Taste Masking of Orodispersible Films: A Case Study in Palatability Optimization