Purpose: Extended-release (ER) formulations are widely used to reduce dosing frequency and maintain a desired therapeutic effect over a longer duration. Many nutraceutical products are formulated as immediate release and maximum absorption of the active ingredients achieved by ingestion of several spaced doses throughout the day. However, to improve consumer compliance and better dosing effect, it is beneficial to develop ER formulations for nutraceutical formulations. Vitamin C is water-soluble, well recognized for the vital role it plays in supporting immunity and is available in various dosage forms. The ER formulations of vitamin C are mainly used to treat scurvy or prevent deficiency [1]. The required daily dose of vitamin C ER tablet formulation varies from 500 mg to 1.5 g [2,3]. From a formulation perspective, vitamin C presents tableting challenges due to its poor flow, low compressibility, and high dose for ER matrices. The purpose of this work was to develop and study a high dose vitamin C (1000 mg) ER tablet formulation using a hydrophilic matrix system coated with a moisture barrier film coating system, with an 8-hour release profile. Methods: Vitamin C (1000 mg) ER tablets were prepared using high shear granulation with Starch 1500®, partially pregelatinized starch as a binder. METHOCEL™ K100LV Premium was used as the extended-release excipient. The formulation composition is outlined in Table 1. Manufacturing of Tablets Using High Shear Granulation
Method: Vitamin C and METHOCEL™ K100LV were passed through ASTM #40 screen. The granulation dispersion of Starch 1500 was prepared in water (room temperature) at 20 % w/w solids. Dry mixing of the intragranular blend was performed in a rapid mixer granulator (Bowman and Archer, 2L, India) at low impeller speed followed by wet massing using the Starch 1500 dispersion. Wet granules were dried in an oven at 30-35°C to achieve a loss on drying (LOD) of not more than 2.0. The dried granules were passed through a multi-mill fitted with a 1.5 mm screen. The extra granular ingredients (METHOCEL™ K100LV, MCC, and colloidal silicon dioxide) were weighed and passed through ASTM #40 screen. Both intra and extra granular ingredients were blended (Rimek Kalweka, India) for 10 mins at 20 rpm followed by lubrication with magnesium stearate, previously passed through ASTM # 60 sieve for 2 mins. The powder blend was tested for powder flow and compressed (Karnavati, Rimek Minipress SF II, India) with 21.5 x10.8 mm, standard concave tooling. Matrix tablets were coated in a perforated coating pan (O’Hara Labcoat LCM) with Nutrafinish® Moisture Protection Coating to 3.0 % weight gain (WG) using 20%w/w solids in water. Tablet Testing: Physical properties were tested: weight, hardness, thickness, friability after 100 rotations in a USP friabilator, assay and dissolution profile using 900.0mL phosphate buffer, pH 3.0, paddle method using a sinker, at 50 rpm for 12 hours. Stability Testing: Coated tablets were packaged in 100 cc HDPE bottles and subjected to stability evaluation for 3 months, at 30°C/65% RH and 40°C/75% RH storage conditions and tested for assay and dissolution profile. Results: The powder blend showed satisfactory properties for rotary compression in comparison with API and blend uniformity. Tablet Physical Properties: Vitamin C ER Tablets showed good hardness ~16 kP and low friability of ~0.33% at 100 rotations. Coated tablets were smooth and elegant in appearance (Figure 1). Drug assay and dissolution profile: A drug assay of 98-100% was achieved for uncoated and coated tablets. Matrix tablets showed a consistent 8-hour drug release profile. Stability Testing: The physical appearance of tablets coated with the Nutrafinish moisture barrier coating showed no signs of discoloration following the 3-month 40⁰C/75% RH stability study, whereas uncoated tablets showed slight discoloration at the end of 3-month stability. Assay results were consistent with the initial values and there was no significant difference in the drug release profile observed with f2 values of more than 75% (Figure 2). Conclusion: METHOCEL™ K100LV was successfully used as a hydrophilic matrix polymer along with Starch 1500 as a binder to design a high dose (1000 mg) vitamin C ER formulation. Nutrafinish moisture protection coating was successfully used for coating the vitamin C ER formulation which remained stable over the period of 3 months. References: 1. Access online on 10th April 2022. https://reference.medscape.com/drug/ascor-cenolate-vitamin-c-ascorbic-acid-344416 2. Mark Levine, Cathy Conry Cantlena et al. Vitamin C Pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Medical Sciences Proc. Natl. Acad. Sci. USA. Vol 93. pp.3704-3709, April 1996. 3. Access online on 28th April 2022. https://reference.medscape.com/drug/ascor-cenolate-vitamin-c-ascorbic-acid-344416
Table 1. Composition of Vitamin C ER 1000 mg Tablets
Figure 1. Photographs of Vitamin C ER Uncoated and Coated Tablets
Figure 2. Drug Release Profiles of 1000 mg Vitamin C ER Tablets at Initial and 3M Stability Time Points
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