TABLET REFORMULATION CASE STUDY. Executive Summary

Size: px

Start display at page:

Download "TABLET REFORMULATION CASE STUDY. Executive Summary"

Brittany Waters
8 years ago
Views:

1 TABLET REFORMULATION Executive Summary A large European pharmaceutical company contracted Aptuit to reformulate a tablet with existing dosage strengths of 25 mg and 50 mg. The client required smaller strengths of 0.1, 0.5, and 1, 1.5, 2.5, 5 and 10 mg. Using the existing Active Pharmaceutical Ingredient, Aptuit needed to develop all of the smaller strengths with a tablet core weight of 100 mg. The five-year study was led by Project Management, with substantial support from a manufacturing supervisor. The latter brought specific formulation expertise related to the transfer of materials to the manufacturing stage of development. The rest of the Aptuit team was comprised of additional formulation experts, analysts and manufacturing professionals. The very low concentrations in the 0.1 mg and 0.5 mg dosage forms required the development of a geometric mixing process to address potential uniformity issues. Throughout the compression process, it was necessary to test the samples for content uniformity to facilitate transfer to Aptuit s clinical trials manufacturing group. As a result of the concerted effort of the Aptuit team, all dosage strengths were successfully developed and transferred to Aptuit s Clinical Trials manufacturing site. 1

Using the existing Active Pharmaceutical Ingredient, Aptuit needed to develop all of the smaller strengths with a tablet core weight of 100 mg.

2 The Challenge Aptuit was challenged to address the potential obstacles to content uniformity in a large group of samples with dosage strengths in a range from 0.1 mg to 10 mg. Accordingly, Aptuit needed to devise unique compression techniques. Throughout the initial compression studies, Aptuit was challenged to test these tablet runs for content uniformity and label strength. The Aptuit Solution A workflow chart (Figure 1) demonstrates the process that led to developing granules for compression. API (Dose Strengths mg) Diluent Geometric mixing Add Binder, Diluent and Disintegrant Dry Blend Materials in Niro Fielder PMA 65 Granulator Bowl Dry Wet Mass in Aeromatic Strea-5 Wet Granular using a Suitable Concentration of Granulation Fluid Mill Granules using J&C No.5 Oscillating Granulator Add Extra-granular Disintegrant and Lubricant Blend Materials using Winkworth Drum Blender Figure 1 2

Throughout the initial compression studies, Aptuit was challenged to test these tablet runs for content uniformity and label strength.

3 Compression Technique Aptuit used the existing clinical formulation to redevelop the various dosage strengths requested. A Manesty F3 single station press (Figure 2) was employed as well as Manesty D3B rotary presses. Figure 2 The work flow of the process (Figure 3) included testing of stratified samples for content uniformity and testing of samples for weight, hardness, thickness, flexibility and disintegration. The process involved a wet granulation which was compressed using a 6 mm round normal concaved tooling. Tablets were then coated with a HPMC-based film coat. Compression on Manesty D3B using 6 mm RNC Tooling to Tablet Weight of 100 mg Stratified Samples taken at 10 Equal Points for Content Uniformity Testing Samples Taken for In-process Testing (Weight, Hardness, Thickness, Friability and Disintegration) Tablet Cores Film Coated using Manesty Accelacota Drum Coater to Target Weight Gain of 4 % w/w Figure 3 3

Figure 2 The work flow of the process (Figure 3) included testing of stratified samples for content uniformity and testing of samples for weight, hardness, thickness, flexibility and disintegration.

4 Dissolution Profile Dissolution profiles were assessed for the new reformulated lower doses of 0.5 mg and 5.0 mg as shown in Figure 4. The reformulation of the lower dose tablets did not compromise the release of the API from the tablet matrix as demonstrated by the similar profiles depicted in Figure 4. Figure 4 Riccarton Process Development The reformulation of the reduced tablet strengths were conducted at the Riccarton site, Aptuit s Formulation Development laboratories in Edinburgh, Scotland (Figure 5). The process was then successfully transferred to Aptuit s Clinical Trials manufacturing site in Livingston, Scotland. Figure 5 4

5 Conclusion Aptuit successfully developed all of the dosage strengths, ensuring homogenous distribution of the API in every form and maintaining the desired core weight for all of the tablets across the range of 0.1 to 10 mg. The client found added value in the minimal waste of the API throughout the project. They were impressed with the special techniques and procedures that Aptuit initiated to achieve stability, content uniformity and the seamless transfer to clinical trial manufacturing. Throughout the entire process, the client reported that excellent, ongoing communications from Project Management was a strong reassurance that the project was on track and would be completed on time. At Aptuit, it s all about the science. 5

They were impressed with the special techniques and procedures that Aptuit initiated to achieve stability, content uniformity and the seamless transfer to clinical trial manufacturing.

STARCH 1500. Application Data

STARCH 1500. Application Data STARCH 1500 Application Data Partially Pregelatinized Maize Starch Starch 1500, Partially Pregelatinized Maize Starch, Used as a Binder Disintegrant in High Shear Wet Granulation Comparison to Povidone