A Process Development and Validation of Mirabegron Extended Release 25 Mg and Silodosin 8mg Bilayer Tablet

Abstract

Introduction: Mirabegron & silodosin, is used often in combination as bilayer tablets, are primarily used to treat the symptoms of overactive bladder (OAB) & benign prostatic hyperplasia (BPH). Mirabegron drug helps to relax bladder muscles by increasing urine storage capacity and reduction in urine urgency. . The drug Silodosin helps to relax the muscles in the prostate and bladder neck by improving urinary flow and reducing BPH-related symptoms. The aim of the research study is to process validation (PV) of the formulation development of bilayer tablet of Mirabegron & silodosin drug.  Process validation batches were manufactured for the demonstration of the process performance for reproducibility and consistency within its range of operation as per process design. Mirabegron to be manufactured in extended-release form for prolonged action and silodosin in immediate release form.Based on the results of the validation process, the observed results indicate that the process design for the manufacturing of the product, mirabegron and silodosin tablet 25mg & 8 mg is found to be robust enough for manufacturing of a quality drug product.These validated products give the specified quality attribute results & meet all the predetermined specification criteria. The PV study highlights the potential of a Mirabegron ER & Silodosin bilayer tablet approach, combining immediate release & Extended-release formulation, for creating an extended-release dosage formmirabegron & immediate release dosage form of silodosin.

Objectives: The main objective of  Process validation of Mirabegron 25 mg (ER) & Silodosin 8 mg Tablets is for attain the critical quality attributeswithin the specified limit and to validate the process parameters as per the quality standards.

           Objectives of bilayer tablets:

• It is possible to integrate one or two distinct active medicinal substances.


• Additionally, they are employed to separate incompatible active medicinal components.


• By sandwiching, the API layer's surface area is altered. One or two inactive layers can regulate it and cause it to reach the erodible or swellable barriers for modified release.


• It is employed to fix a mixture of various active medicinal components. The drug product's life cycle is extended.

Methods: The formulations are designed for bilayer tablets combining IR (immediate release) and ER (Extended release) components in differentratios. Each drug layerhasitsseparategranulationprocedure. For the preparation of Immediate Release (IR) granules, Silodosin, microcrystalline cellulose, lactose monohydrate, and SSG (sodium starch glycolate) were mixed with an inactive binding solution, whichispovidone-90dissolvedinpurifiedwater,usinga high-speed mechanical stirrer.After mixing solutions in dry powder, the wet granules were dried using an FBD. Dried granules were further sized using the 1.0 mm mesh and lubricated with magnesium stearate and Aerosil/colloidal silicon dioxide.For the preparation of SR granules, mirabegron, lactose, starch and HPMC K4 passedthroughthe sieve and further binding done by using PVPK-90. The dry powder was mixed in RMG, and further binding has been done by the binding agent and dried by using FBD 120 kg. Dried granules sized by 1.0mmmeshandmixedusingDouble cone Blender 185 ltr capacity. After mixing, the granules were lubricated with magnesium stearate (Jadiya et al., 2024).The both layergranuleswere further compressedtoform the bilayertabletsconsistingofImmediate Release andSustained releaselayers using an Cadpress IV compression machine using the round shape plain punches.The compaction pressure was set at 10 kN, to achieve the required hardness of tablets during the process of compression.The batch size was 2.0 lac tablets.After forming the bilayer tablets, the tablets were further coated with Opadrycoating material using a solace auto coater 37” capacity.

Results: The all physical and chemical analysis results are evaluated as per the protocol and parameters

Conclusions: Based on summary report and observed result at different stage, it is concluded that process validation of Mirabegron 25 mg (ER) & Silodosin 8 mg Tablets was carried out as per respective protocol and observed results of critical process parameters and critical quality attributes were found within the specified limit. Finished product results of batch were found within the specified limit.