(T1530-03-18) Application of Hypromellose Phthalate (HPMCP) for the development of Esomeprazole 20mg Multiple Unit Pellet System (MUPS)

Purpose: To develop Esomeprazole 20mg MUPS tablet formulation using Hypromellose Phthalate (HPMCP HP-55S) as an enteric coating polymer and SmartEx (QD-100) as a cushioning agent which complies to USP specification of Esomeprazole capsule.

Methods: Method to develop Esomeprazole 20mg MUPS tablet is described below. Drug layering → Seal Coating → Enteric coating → MUPS tablet. Fluid Bed processor (GPCG 1.1) Wurster approach is used for the development and 400g material is taken for processing at each step. Drug Layering: Sugar spheres of mesh size # 45-60 (250-355 µm) were drug loaded with 17.0 % w/w Esomeprazole aqueous dispersion, Hypromellose 6 cps (Pharmacoat^® 606) is used as a binder. Refer Table 01 for drug layering ingredients and their concentrations. In process parameters are inlet air flow is 60-70 CFM, inlet air temperature is 41-44^oC, product temperature is maintained between 33-35^oC, inlet RH is 27-28%, nozzle diameter for spraying coating suspension is 1mm, spray rate is 1-4 g/min with atomising pressure kept at 1.4 bar. Seal Coating: Drug loaded pellets were given seal coating (barrier coating) to avoid interaction with enteric polymer. For seal coating, Hypromellose 3 cps (Pharmacoat® 603) is used as a film forming polymer. 50% polymer weight gain is done in seal coating layer. Refer Table 01 for seal coating layer ingredients and their concentrations. In process parameters are inlet air flow is 70-90 CFM, inlet air temperature is 38-41^oC, product temperature is maintained between 38-40^oC, inlet RH is 26-28%, nozzle diameter for spraying coating suspension is 0.8 mm, spray rate is 1-7 g/min with atomising pressure kept at 1.4 bar. Enteric Coating: Seal coated pellets were then coated with enteric coating polymer- Hypromellose Phthalate (HPMCP) HP-55S with incorporation of talc and plasticizer in the solution. For enteric coating layer, polymer weight gain is 60%. Refer Table 01 for enteric coating ingredients and their concentrations. In process parameters for enteric coating are inlet air flow is 70-90 CFM, inlet air temperature is 31-35^oC, product temperature is maintained between 31-33^oC, inlet RH is 21-23%, nozzle diameter for spraying coating suspension is 0.8 mm, spray rate is 1-3 g/min with atomising pressure kept at 1.5 bar. Enteric coated pellets were checked for dissolution in acidic environment which passes USP criterion. MUPS Tablet: Enteric coated Esomeprazole pellets were mixed with SmartEX (co-processed excipient of D-Mannitol, Low substituted hydroxy propyl cellulose and Polyvinyl Alcohol) which is a cushioning agent and L-HPC LH-11 which functions as an anti-capping agent in this formulation. The performance of Esomeprazole MUPS tablets was checked as per USP for Esomeprazole capsules. Formula composition is given in table no. 01.

Results: Enteric coated Esomeprazole pellets and compressed MUPS tablets were subjected for in process testing and evaluation. Enteric coated pellets and MUPS tablets showed the acid resistance in pH1.2 in 2 hours and gave complete release in pH 6.8. MUPS tablet hardness was 90-100N, Compression force was 23.3KN, Tablet thickness is 5.4-5.5mm.
Scanning electron microscopy (SEM) and dissolution study was conducted and found satisfactory as per USP specifications. Refer Fig. No. 01 and Fig. No. 02 for results.

Conclusion: Esomeprazole 20mg MUPS tablet formulation was developed successfully using Hypromellose phthalate (HPMCP HP-55S) as an enteric coating polymer and SmartEx (QD-100) as a cushioning agent during tablet compression. The developed formulation possesses resistant to acidic pH with a desired release profile in buffer medium as per USP dissolution specification. The formulation as well as process parameters for various coating process (drug layering, seal coating, enteric coating) were optimized and stable.

Table 01: Esomeprazole 20mg MUPS formula composition

Fig. No. 01 Cross section of MUPS and SEM analysis of Esomeprazole enteric coated pellets

Fig. No. 02 In vitro release study of Esomeprazole Enteric coated Pellets and MUPs formulation