Evaluation of Oral Strips for Enhanced Water-Soluble Vitamin Delivery for Vitamin B12

Vitamin B12 is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication. Because vitamin B12 contains the mineral cobalt, compounds with vitamin B12 activity are collectively called cobalamins (Figure 1) (1). Methylcobalamin and 5-deoxyadenosylcobalamin are the metabolically active forms of vitamin B12. However, two others forms, hydroxycobalamin and cyanocobalamin, become biologically active after they are converted to methylcobalamin or 5- deoxyadenosylcobalamin (2).

Figure 1: Vitamin B-12 (Cobalamin)

Vitamin B12 is required for the development, myelination, and function of the central nervous system; healthy red blood cell formation; and DNA synthesis (3). Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase catalyzes the conversion of homocysteine to the essential amino acid methionine. Methionine is required for the formation of S-adenosylmethionine, a universal methyl donor for almost 100 different substrates, including DNA, RNA, proteins, and lipids. L-methylmalonyl- CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the metabolism of propionate, a short-chain fatty acid (4, 5). The study aims to design and evaluate oral strips for improved Vitamin B12 delivery using various polymers and technologies. It will focus on developing physicochemical properties, mucoadhesive strength, and in-vitro release. The study will also investigate the impact of formulation parameters on Vitamin B12 delivery, optimize formulation and process parameters, compare the performance of developed oral strips with conventional systems, explore the potential of oral strips for digital health technologies, and contribute to the development of effective oral delivery systems for vitamins and nutrients.

MATERIAL AND METHODS

Preformulation Studies

The drug samples were examined for appearance, color, and odor. The melting point of Vitamin B12 was determined using the capillary method, where a fine powder of the drug was filled in a glass capillary tube and dipped in liquid paraffin. Solubility was also determined in various buffers of different pH values, with the drug being dissolved in different beakers containing solvents and shaken for 24 hours at regular intervals. The drug was identified using UV spectroscopy, where a calibration curve was prepared by dissolving anhydrous disodium hydrogen phosphate and potassium dihydrogen phosphate monohydrate in water. The drug was then transferred into a volumetric flask and solved in methanol, resulting in a concentration of 200 µg/ml. The drug was then transferred to different flasks, resulting in concentrations of 2,4,6,8,10 µg/ml [6-10].

Preformulation Study

Key parameters evaluated during pre-compression include bulk density, tapped density, Hausner's ratio, and Carr's index, which provide insights into the flow properties and compressibility of the powder blend. Moisture content and particle size distribution also play a significant role in determining the stability and release profile of omeprazole within floating matrices (11, 12).

Formulation Development of Vitamin B 12 Mouth Dissolving Film

Solvent casting method was used for preparation of film [13-16]. The formulation of a Vitamin B12 mouth dissolving film involved soaking a polymer in a solvent overnight, mixing it on a magnetic stirrer for 30 minutes, adding plasticizer, film modifier, and sweetening agent, and sonicating it for 30 minutes. The solution was then poured into a circular petriplate, lubricated with glycerin. The films were dried at room temperature, peeled, cut into 2cmx2cm films, wrapped in butter paper, and stored in a desiccator. The film's quality attributes included clarity, peelability, stiffness, and disintegration time. Water was chosen as the solvent due to its high solubility in water, but the film's drying time was prolonged. Cosolvent ethanol was used to reduce the film's drying time. Various film forming polymers were screened for their film forming ability, with HPMC being the best. The solvent casting method was used to prepare the films. HPMC produced transparent, non-sticky films, while PEG 400 produced sticky films. Maltodextrin and honey were used to produce translucent and transparent films. The formulation F1-F5 was chosen based on placebo trials (Table 1).

The prepared films were evaluated for physical appearance, microscopy, weight, thickness, surface pH, folding endurance, disintegration time, tensile strength, drug release and stability [17-19].

RESULTS AND DISCUSSION

Preformulation Studies

Organoleptic characteristics of the Vit B12 was examined by using sense such as eyes, touch and smell (Table 2). The Indian pharmacopeia recommended the capillary method for melting point determination, and the standard melting point of drug was found to be 377.36°C, within the reported range of 375–379°C, indicating the drug sample's purity. Solubility check is also a key parameter in drug development as it determines the ability of a drug to dissolve in various

solvents. This information is crucial for designing dosage forms that ensure optimal absorption and bioavailability of the drug. Vitamin B12 is a water soluble vitamin.

Table 2: Identification and Characterization of Vitamin B12

Calibration curve of Vitamin B12

The scan of Vitamin B12 solution in UV region (200-400) was performed to check the wave length of maximum absorption (? max). The ?max was found to be at 547 nm. Hence calibration curve of Vitamin B12 was constructed at 247 nm in pH 6.8 phosphate buffer by taking concentration on x-axis and absorbance on y-axis (Table 3; Figure 2). The calibration curve shown the regression coefficient of 0.999 and found to be linear in the concentration range of 2 to 10 µg/ml.

Figure 2: Calibration curve of Vitamin B12 (at 547 nm) in pH 6.8 phosphate buffer

The films were homogenous and transparent, with good brittleness. The weight variation of 2 cmx2 cm2 films from different batches was within prescribed limits. The surface pH ranged from 6.3-6.7, avoiding irritation to the oral mucosa. The drug content varied between 95 and 99.50, indicating a uniform distribution of atenolol in the formulated films with complete solubilization. The percentage drug content varied between 95 and 99.50, indicating a complete solubilization of the drug. The results suggest a uniform distribution of atenolol in the films.

All the formulations batches were subjected to in-vitro drug release studies using 0.1 N HCI. The present drug release of all formulation was determined in 0.1 N HCI at the interval of 1 to 10 minutes. Among all formulations, F1 formulation containing highest concentration of superdisintegrant and sublimating agent showed maximum drug release within 5 minutes compared to other formulations (Figure 3).

Figure 3: Invitro Drug Release

Stability Studies

Stability Study of Optimized Batch (F1) is shown in Table 5. As per the data, it was concluded that tablet dosage form was stable enough till 6 months under the accelerated conditions as per the ICH.