(T1330-07-47) Fast-Dissolving Oral SMEDDS Films: A Novel Platform for Enhanced Delivery of Vitamin D3

Purpose: Vitamin D is well-established as a crucial regulator of calcium homeostasis and bone metabolism and mineralization. Vitamins D2 and D3 are the two main types of Vitamin D. It is used to prevent and treat bone diseases like rickets, osteomalacia, and osteoporosis. Furthermore, a substantial growth in the evidence that supports the positive influence of this vitamin on the regulation of the immune response, suggesting benefits ranging from protection against respiratory tract infections to the prevention and management of asthma. Vitamin D deficiency is widespread, affecting not only vulnerable groups like the elderly and hospitalized (with 60% and 57% deficiency rates respectively in US studies) but also a significant portion of healthy young adults (nearly two-thirds in a Boston study at winter’s end). National data from 2001-2018 in the US revealed that 2.6% had severe deficiency, 22.0% moderate deficiency, and 40.9% insufficiency, with vitamin D levels fluctuating seasonally. The currently available medications include capsules and soft gels, liquid solutions and tablets. Vitamin D3 belongs to BCS class II, with low solubility and high permeability. The objective of this study was to develop and evaluate the SMEDDS based oral mouth dissolving film for Vitamin D3 which would enhance the solubility of Vitamin D3 thereby providing rapid disintegration and dissolution and to improved patient compliance especially for dysphagic patients.

Methods: In this study, initially SMEDDS were prepared using ABISOL™ V as emulsion pre-concentrate containing mixture of oil surfactant and co-surfactants. ABISOL™ V was selected as it eases the preparation of SMEDDS and has HLB value 9.9 which is suitable for further development of oral films. The films were prepared by solvent evaporation technique. The Polyox N750 was used as polymer, as it has excellent film forming properties, provides non gritty mouthfeel with rapid hydration and dissolution. PEG 400 was used as the plasticiser to enhance the flexibility and the mechanical properties of the film. Butylated hydroxy toluene (BHT) and citric acid were added as antioxidants to stabilize the formulation. Additionally, citric acid and sucralose were added as saliva stimulating agent and sweetener respectively. The optimized formulation was further evaluated for weight variation, thickness, and folding endurance.

Results: The optimized Vitamin D3 SMEDDS based mouth dissolving film provided promising properties. The SMEDDS were evaluated for the particle size and zeta potential. The particle size i.e. the Z average was found to have desired size of 147 nm with 0.233 polydispersity index indicating stable SMEDDS formulation. The films were cut into 2cm x 2cm size and evaluated. The weight variation for the film was found to be 65.13 ± 1.76 mg. The coefficient of variation of approximately 2.70% indicates a low relative variability in the weights of the film. The films showed 0.163 ± 0.015mm thickness. The folding endurance was found to be more than 200 which promises films with good flexibility and robustness. Additionally, the films showed rapid disintegration within 40 seconds. While initial characterisations were promising, the assay studies and in-vitro release study are currently underway.

Conclusion: The formulated Vitamin D3 Self-Micro-emulsifying Drug Delivery System (SMEDDS) integrated into a mouth-dissolving film presents an innovative approach to vitamin D3 combining the benefits of enhanced drug solubilization offered by SMEDDS with the convenience and rapid delivery through fast disintegration and dissolution of an oral thin film. This promising combination holds significant potential for improving vitamin D3 supplementation and addressing widespread deficiency.

References: 1. Vin Tangpricha, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP. Vitamin D Deficiency and Related Disorders. Updated: Sep 19, 2024, Medscape.
2. Dangre PV, Gurram NJ, Surana SJ, Chalikwar SS. Development and optimization of vitamin D3 solid self-microemulsifying drug delivery system: investigation of flowability and shelf life. AAPS PharmSciTech. 2022 Apr 11;23(4):110.


Figure 1: Particle size analysis of the SMEDDS.