Preliminary Study on the Development of Orodispersible Film containing Desloratadine

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Objectives: Orodispersible films (ODFs) are new-generation dosage forms that increase patient compliance, providing ease of drug administration in many patient groups, such as pediatric, geriatric, and patients with physiological and psychiatric disorders.The purpose of this study was to conduct preliminary studies to develop ODF containing the poorly water-soluble and oxidation-sensitive drug desloratadine (Dl). Materials and Methods:In this study, the formulation and process parameters as well as the characterization method were investigated using 20 film formulations manufactured by the solvent casting method.The films were characterized in terms of their appearance, mechanical properties, thickness, disintegration time, and content uniformity.Various strategies have been applied in order to increase the chemical stability of Dl in the formulations and therefore to choose suitable antioxidants, and morphological and compatibility studies using dynamic stability control were performed.For increasing drug loading, different film compositions were also evaluated.Results: Among the preliminary formulations tested with a casting height of 400 µm homogeneous, good mechanical properties with tensile strength values between 6.21-10.34MPa, flexibility, and ODFs with a disintegration time less than 60s ODFs were developed.By increasing the solubility of Dl in the formulation with the selected components, the drug loading capacity was increased to 3% by the desired level.Conclusion: One of the enabling formulations, F20, was particle-free with a suitable thickness uniformity (relative standard deviation=4.6%)and content uniformity (acceptance values=5) films were developed.Keywords: Orodispersible film, solvent casting method, desloratadine films.5 The type and concentrations of film-forming polymers that form the main component of orally disintegrating films are largely responsible for producing films with appropriate mechanical strength and integrity.5,6 Films are manufactured using different methods such as hot melt extrusion, electrospinning and solvent casting method.3 Among these methods, the solvent casting method is the most widely used in the pharmaceutical industry due to its simple production process and low cost.7 Polymers used in ODFs can basically be classified as cellulose derivatives, starch derivatives, synthetic, and semi-synthetic polymers.Starch derivatives are among the most preferred polymers among all natural biopolymers because of their low price, widespread availability, and biodegradability.Modified starches used in oral films include maltodextrin (Maltrin ® , Maltodextrin ® ), hydroxypropyl pea starch (Lycoat ® ), pregelatinized starch (Instant Pure Coat ® ) and Pullulan.6 Of the cellulose derivatives, hydroxypropylmethylcellulose (HPMC) and hydroxypropyl cellulose (HPC) are most commonly used as film-forming polymers.Other commonly used excipients in the production of ODF include plasticizers (glycerol, propylene glycol (PEG), sorbitol, polyethylene glycol), fillers (maltodextrin, mannitol), saliva enhancers (citric acid), solvents, color, flavor, stabilizer, surfactants, and various solubility enhancing agents (CD derivatives, Kleptose ® linecaps) depending on the product's quality target product profile and the active ingredient used.1,2,6,8 Another factor that may affect mechanical strength is morphological changes in the films, such as crystal formation caused by the active ingredient.9 Therefore, for mechanical strength in films, in addition to the filmforming materials, different factors, such as the type and amount of active substance in the film, the thickness, and the manufacturing process must be carefully controlled.5 Desloratadine (Dl) is a 2nd generation H1 antihistamine that is widely used in the treatment of allergic rhinitis and urticaria.The recommended oral dose is 5 mg for adults and adolescents.For the pediatric population from 1 to 5 years old, 1.25 mg of XXX can be administered once a day, whereas children aged between 6 and 11 years may be administered 2.5 mg of XXX once daily.10 Dl is currently available in the market in the form of a 5 mg film-coated tablet, as well as an oral solution suitable for use at lower doses in pediatric patients and in certain patient groups.The development of an orodispersible film formulation for Dl provides several advantages over traditional formulations, including enhanced patient compliance, decreased risk of choking, mitigation of stability issues associated with liquid formulations, and accurate dosing.With the growing focus on personalized medicine, ODFs offer the advantage of dose-specification.These formulations can be tailored in terms of dose and size to suit individual age and physiological conditions, facilitating individualized treatment and improving therapeutic outcomes.Given the advantages of ODFs and the necessity to overcome the issue of low drugloading capacity in this dosage form, we aimed to develop a formulation containing 5 mg of Dl that aligns with the highest recommended dosage and ensures therapeutic efficacy.Dl is practically insoluble in water.11 Moreover, due to its molecular structure, Dl is prone to degradation and is especially sensitive to oxidation.12,13 Considering the properties of the active substance, the aim of the present study was to evaluate the appropriate formulation composition, process determination, and characterization methods through preliminary formulation development studies for Dl-containing ODF. Materials and Methods MaterialsDl was a gift sample from Nobel İlaç.Citric acid anhydrous (10024) was obtained from Merck.Pregelatinized hydroxypropyl pea starch (Lycoat RS 780 and Lycoat RS 720), pea maltodextrin (Kleptose Linecaps), and maltodextrin (Glucidex IT6) were kindly donated by Roquette Pharma.HPMC E15 and HPMC E5 (Methocel E15 LVP, Methocel E) were supplied by colorcon.HP-β-CD (Cavasol W7 HP Pharma) was gifted by Ashland.Sodium methionine, ascorbic acid, and EDTA were procured as gift samples from Drogsan.Propylgallate was kindly supplied by Ali Raif Pharmaceuticals.Polyvinylpyrrolidone (Kollidon ® 30 LP), PEG 400, and poloxamer (Kolliphor ® P188) were obtained from BASF.Ethanol absolute (Merck) and propylene glycol (PG) (Merck Emsure) were purchased from local vendors.All other reagents and solvents were of analytical grade. Method Compatibility StudyDifferential scanning calorimetry (DSC) analyses were performed on 2 mg samples of Dl, excipient, and drug: excipient in a ratio of approximately 1:1 (w/w) and were weighed and placed in aluminum sample containers.After closing the aluminum cover and compressing it with pressure, the cover was placed in the heating cell of the instrument (Shimadzu, DSC-60, Japan).Measurements were performed in the temperature range of 25°C-300°C at a heating speed of 10°C/min under a nitrogen atmosphere.ODF preparation ODF was prepared using the solvent casting method.The quantitative compositions of the formulations are listed in Table 1.The ODF preparation steps are illustrated in Figure 1.According to the procedure for the preparation of the polymer solution, film-forming enhancing agents and plasticizers were first added to a measured amount of water, which was heated to 90°C when using HPMC polymer, and then mixed until a homogeneous solution was obtained.In a separate beaker, solubility-enhancing agents, antioxidants, ethanol, Dl, and other excipients u n c o r r e c t e d p r o o f