Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate

Transcription

1 Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate Ready-to-Use High Functionality Excipient Composite Offering Advantages for Total Cost Savings Superior Quality Easier Handling Fast Time to Market

2 Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate Introduction Technology The health science industry faces a wide variety of challenges including increased pressure to: Reduce costs Accelerate time to market Improve product performance These challenges drive health science companies to find new solutions for improving time- and cost-efficiency in oral dosage form development and production. Formulation scientists developing direct compression formulations generally require several conventional excipients often at high levels to obtain good material flow, compaction, blending properties, content uniformity, carrying capacity, stability, lubricity, and disintegration. Finding the proper excipient combinations and concentrations to achieve adequate solid dosage formulas is a time-consuming, and often expensive process, that varies with active pharmaceutical ingredient (API) characteristics. was developed to provide an innovative solution to meet these challenges. Beyond its benefits in conventional batch production, presents a set of properties that make it well-suited for continuous processing. Because it acts multifunctionally as a filler/binder, flow aid, disintegrant, and lubricant at the same time, production requires only two feeders. This not only leads to space saving, but also helps to simplify control of the production process. EASYtab's unique surface structure and good flowability enable fast and segregation-free blending with APIs. Its all-in-one structure, using sodium stearyl fumarate as a lubricant, provides outstanding robustness in terms of blending times. Regular MCC with Smooth Surface Areas Micro-Rugosity Introduced by Technology Compounding with Technology leads to a homogeneous distribution of the individual components throughout the particle and on its surface. The synergistic effects achieved by this technology include better compactability, flowability, and content uniformity, due to a significantly increased surface area. What is? was developed using JRS Pharma s proven Technology and is the first lubricated high functionality excipient on the market. is an all-in-one, ready-to-use excipient composite. It effectively combines four individual components. Function / Content Regulatory Status Ingredient Pharma Binder / Filler Microcrystalline Cellulose 96 % Ph. Eur., NF, JP CAS No Superdisintegrant Sodium Starch Glycolate 1.2 % Ph. Eur., NF, JP CAS No Glidant Colloidal Silicon Dioxide 2 % Ph. Eur., NF, JP CAS No Lubricant Sodium Stearyl Fumarate 0.8 % Ph. Eur., NF, JPE CAS No Tab

3 Streamline Your R&D and Production is more than a simple physical blend. It is a homogenous, lubricated high functionality excipient composite. Each component of the composite maintains its chemical identity while synergistically providing increased functional performance. Ingredients of Colloidal Silicon Dioxide (CSD) Bulk Density 40 g/l Average Particle Size 12 nm Sodium Stearyl Fumarate (SSF) Bulk Density 240 g/l Average Particle Size 16 µm physical blend Sodium Starch Glycolate (SSG) Bulk Density 730 g/l Average Particle Size 50 µm Microcrystalline Cellulose (MCC) Bulk Density 320 g/l Average Particle Size 100 µm MCC CSD SSF SSG Physical Blend of the four components Heterogeneous mixture Risk of segregation No improvement of surface area and structure Homogeneous, monoparticulate composite High functionality excipient Enhanced flowability 100 % larger surface area 3

4 Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate Comparison with Physical Mixture Particle Size Distribution T [%] EASYtab Physical Mixture Diff. Volume [%] EASYtab Physical Mixture Fig V* [cm-1] Comparison of the IR Spectra after Co-Processing 1 0 0,3 0,5 0,7 1,1 1,6 2,4 3,5 5,1 7,4 10,7 15,6 22,7 33,0 47,9 69,6 101,1 146,8 213,2 309,6 449,7 653,0 948,3 Particle Size [µm] Fig. 2 Particle Size Distribution of and the Corresponding Physical Blend of the Individual Components. 1377,0 2000,0 Physical Properties of Stability Data Parameter Physical Mixture Bulk Density [g/l] Angle of Repose [ ] Moisture [%] Spec. Surface Area [m²/g] Tab. 2 Physical Characteristics of a Randomly Selected Lot of. The Large Surface Area of Enables Efficient and Segregation-Free Blending. Parameter/ Specification 0 Month 1 Month 3 Month 6 Month Loss on Drying (Ph.Eur , 5.1 % 4.7 % 5.0 % 5.0 % 105 C, 3h) Tab. 3 In Sealed Original Packaging, under ICH Stress Conditions 40 C/ 75 % Relative Humidity Moisture Absorption Product Moisture [%] Fig Time [h] 80 % Relative Humidity 60 % Relative Humidity 40 % Relative Humidity 4

5 Case Studies Folic Acid Direct Compression Tablets Direct compression of low dosage APIs often leads to content uniformity issues. The unique Technology used to produce creates a 100 % increase of the specific surface area compared to the physical blend. This, along with its microrugosity, promotes high content uniformity with low dosage APIs. Formulation Physical Physical Mixture Mixture Folic Acid [%] [%] VIVAPUR 102 Microcrystalline Cellulose [%] EXPLOTAB Sodium Starch Glycolate [%] PRUV Sodium Stearyl Fumarate [%] Colloidal Silicon Dioxide [%] Total Content Uniformity RSD [%] Tab. 4 Case study: Folic acid Tablets (8 mm, 100 mg) were pressed on a IMA Kilian Pressima 13EU-D. Piroxicam Direct Compression Tablets Materials Piroxicam VIVAPUR 102 Microcrystalline Cellulose VIVASTAR P Sodium Starch Glycolate PRUV Sodium Stearyl Fumarate Colloidal Silicon Dioxide Total Content Uniformity RSD [%] Formulation 1 Formulation 2 Physical Mixture [mg] [%] [mg] [%] Tab. 5 Case study: Piroxicam Tablets (8 mm, 200 mg) were pressed on a IMA Kilian Pressima 13EU-D Single Composite Excipient Particle Multi-Component Physical Mixture Piroxicam Piroxicam Clumps SEM, x1000 SEM, x1000 Piroxicam Embedded in Physical Mixture Plus Piroxicam 5

6 Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate Case Study Medium- and High-Dose Formulations Results In these formulations, the properties of the API dominate the formulation and compaction properties. A study with 40 % Paracetamol as a poorly compressible model API was performed to investigate the compaction properties of in a challenging formulation. Tensile Srength [MPa] Fig Physical blend Compaction Force [kn] Compressibility 40 % Paracetamol Formulation more hardness The analyzed tablets showed improved tablet properties in comparison to the tablets made from the physical blend. tablets exhibited 50 % higher robustness (tensile strength). In addition, the lubrication efficiency during the tableting run was, on average, 100 % higher in comparison to the physical blend. The dissolution profiles obtained from the study were similar for both products, supporting the option to change from a regular physical blend formulation to a formulation. Dissolved Active [%] Physical Mixture Ejection Force [N] Fig Physical blend Compaction Force [kn] Ejection Force 40 % Paracetamol Formulation less friction Fig Time [min] Dissolution Profile 40 % Paracetamol Formulation Ideal for Film Coating Due to its unique surface structure, is ideally suited for film-coated tablets. It enables crisp logo definition and excellent film adhesion to the core. Case Study: Poorly compressible API + Paracetamol: 18 minutes Tablets (13 mm, 500 mg) were pressed on a IMA Kilian Pressima 13 EU-D More Information Formulation examples and further case studies (e.g. about probiotics and continuous manufacturing) are available upon request. Please contact your sales rep or visit Conventional Tablet 20 % Paracetamol 79 % MCC 1 % PRUV Tablet with Excellent Logo Definition 20 % Paracetamol 80 % 6

7 Benefits of Convert Technical Benefits into Commercial Success is an ideal excipient composite for modern high-speed tableting equipment. Faster tablet production leads to more efficient output. A 300 % increase in production speed equates to a 2 / cost reduction. 3 is an all-in-one-composite. All necessary excipients are included. Simply add the active ingredients, blend, and compress into tablets. This easy method of tableting allows for shorter development times and, therefore, faster market entry, as well as lower R&D costs. The outstanding compaction properties enable smaller tablet sizes and may boost profitability due to prolonged tooling life. With, buy and store only one excipient instead of five, thus reducing storage and quality control costs. Wet Granulation Weighing & Mixing Wetting (binder) & Granulation Drying + Sieving & Milling Extragranular Addition & Mixing Lubrication Compression Direct Compression Weighing & Mixing Lubrication Compression Direct Compression with Weighing & Mixing Compression further simplifies the process of d irect compression. It requires fewer resources than any other method and leaves less time and room for error and batch loss (Figure 7). Regulatory Information GMO-Free Allergen-Free BSE/TSE-Free Complies with general chapters for residual solvents (USP <467>, Ph. Eur. 5.4) Re-evaluation date: 3 years US DMF available Packaging, Samples, and Storage Packaging 20 kg carton box with MDPE liner bag Pallet 16 carton boxes (320 kg) on Euro pallet (800 x 1200 mm) 20 carton boxes (400 kg) on container pallet (975 x 1175 mm) Sample Sizes 400 g or 2 kg in aluminium bag Fig. 7 Traditional wet granulation is typically complex, requiring a great deal of equipment, human resources, and time. Direct compression is a faster, simpler, and often preferred production process. Disclaimer: The information provided in this brochure is based on thorough research and is believed to be completely reliable. Application suggestions are given to assist our customers, but are for guidance only. Circumstances in which our material is used vary and are beyond our control. Therefore, we cannot assume any responsibility for risks or liabilities, which may result from the use of this technical advice. 7

8 JRS PHARMA Bringing Health Science to Life Products and Services Excipients Family of High Functionality Excipients Binders Functional Fillers Lubricants Thickeners+Stabilizers Carriers Superdisintegrants Calcium Supplements Coatings Biopharma Services First Class Manufacturer of Excipients and Coatings for Tablets Customer Benefits Capsules Fillings Convenience Suspension Stabilization Total Cost Savings Emulsion Stabilization Global Services Granules Innovation GMP Manufacturing Sites Excipients JRS Headquarters Rosenberg, Germany Coatings Biopharma Services JRS Sales Companies JRS PHARMA GMBH & CO. KG Business Unit Excipients Rosenberg (Germany) Phone: _GB_V6_ KE Additionally, dedicated representatives in almost every country.