(M1330-11-73) Impact of Core Excipient Selection to Improve the Stability of a Moisture Sensitive Drug, Acetylsalicylic Acid

Purpose: Acetylsalicylic acid (ASA) has analgesic, anti-inflammatory, and antipyretic properties. The most common adverse effect with long term therapy of ASA is gastric irritation, hence, enteric protection is desirable. ASA is known to undergo hydrolytic degradation to acetic acid and salicylic acid in the presence of moisture and elevated temperature. These challenges can be overcome by the choosing the best excipients. StarTab^®, Directly Compressible Starch, shows excellent flow and superior compressibility on high-speed compression machines¹. As a diluent with good moisture management properties and excellent processability, this makes it a good choice for the direct compression process. The aim of this work is to study the impact of StarTab concentration on stability of ASA delayed release (DR) tablet formulations.

Methods: Three different ASA (75 mg) core formulations with target tablet weight of 180 mg, were prepared using direct compression with varying concentrations of StarTab (Formula 1 with 23%, Formula 2 with 43% and Formula 3 with 58%) along with microcrystalline cellulose and stearic acid as a diluent and lubricant, respectively. Core tablets were seal-coated with a HPMC-based 03K clear Opadry^®, complete film coating system at 2% weight gain using 6% w/w solids in IPA: water (88:12 ratio). The seal-coated tablets were then enteric coated with methacrylic acid-ethyl acrylate copolymer (1:1) based Acryl-EZE^® 93O enteric coating system at 10% weight gain using 20% w/w solids in water. Tablet coating was performed in a 10.5" perforated coating pan (O’HARA Labcoat M5), using a 700 g batch size. Coated tablets were then packaged in 75 cc HDPE bottles, sealed and screw-capped then placed under accelerated stability conditions for 6 months, at 30°C/65% RH and 40°C/75% RH. The coated tablets were then evaluated for enteric test performance, drug release, assay, and free salicylic acid content.

Results: Powder blends of all three formulations showed good flow on the rotary tablet press producing tablets with low weight variation, desired hardness (8-9 kP), thickness and low friability (0.34%) with faster disintegration time ( < 2 minutes). ASA DR tablet formulations 2 and 3 at initial and accelerated stability conditions for 6 M remained intact (acid uptake < 10%) during the acid stage (0.1N HCL) up to 120 minutes each, followed by rapid disintegration ( < 11 minutes) in the buffer stage (phosphate buffer pH 6.8). All three formulations of ASA DR tablets, subjected to dissolution tests showed no significant difference in drug release up to 120 minutes in acid stage, while more than 95% of the drug was released in buffer stage (phosphate buffer pH 6.8) within 90 minutes at initial, as well as 6M accelerated stability conditions. Assay and FSA content of formulations 2 and 3 was found to be > 95% and < 3.0%, respectively after 6M accelerated stability condition. However, tablets of formulation 1 showed lower assay (~93%) and higher FSA values (7.5%) at 6M accelerated stability condition (Figure 1).

Conclusion: ASA DR formulations (1, 2 and 3) were successfully prepared using a direct compression method, with varying concentration of StarTab in the core followed by Opadry 03K clear as the seal coat and Acryl-EZE 93O as the enteric coating. Formulation 3 which contained a higher percentage of StarTab (58%) showed the lowest impurity (FSA) generation following 6 months exposure to accelerated stability conditions and no impact on dissolution and % assay; demonstrating the ability of StarTab to improve moisture stability.

Figure 1: FSA Content of ASA DR Tablets at 40⁰C/75% RH Conditions

Figure 2. Photographs of ASA DR Tablets Following Stability