The binding performance of DFE Pharma Starch

Transcription

1 The binding performance of DFE Pharma Starch MCC Starch Lactose Inhalation Superdisintegrants

2 We are DFE Pharma We are the global leader in excipient solutions. We develop, produce and market excipients for oral solid dose and dry powder inhalation formulations. Our customers are pharmaceutical companies, operating globally, regionally and locally. The pursuit of excipient excellence Excipient excellence is a pursuit that will never be fully achieved. What is excellent today will be outdated tomorrow. That s why to us the pursuit of excipient excellence is a way of life. A source of inspiration. Excipient excellence is what guides us on our way to developing and producing the best possible excipient solutions for our customers. Today, tomorrow, always. Leading in expertise We are here to help you create pharmaceutical products that set the new standard. Leading in supply We are here to ensure you can always produce your products. No matter what happens. Leading in time to market We are here to help you grow by minimising the time to market. We invite you to join us in our pursuit of excipient excellence. Pursuit the act of striving towards an ideal with strong determination.

3 3 Starch Your Starch by DFE Pharma Starches have a proven track record as effective excipients. Together with our solid experience with excipients, we provide this natural product in our excipients product portfolio. Which means you can also use starch s binding performance. Brought to you by DFE Pharma. Starch and starch derivatives are widely used excipients in the pharmaceutical industry and are frequently used in oral solid dosage forms such as tablets, capsules or sachets. Our in-house knowledge of starch enables us to provide high-level support and innovative solutions to specific customer challenges. Our production process and your pharmaceutical end product are important factors that determine the appropriate type of starch to be used in the formulation. For many years numerous pharmaceutical companies have successfully formulated their solid oral dosage forms using our native and pregelatinised starch products. DFE Pharma offers three reliable pharmaceutical-grade starch products: Solani Amylum: native potato starch Prejel PA5 PH: fully pregelatinised potato starch SuperStarch 2: partly pregelatinised starch

4 4 Solani Amylum Native potato starch Description Solani Amylum is a purified potato starch in the form of a white and free flowing powder. Solani Amylum complies with USP NF, Ph. Eur. and JP monographs for native (potato) starch (Figure 1, top). Potato starch is a widely accepted raw material within the pharmaceutical market. In comparison to other starches it has a low protein and fat content. Potato starch is also gluten free and Solani Amylum can be provided with a GMO-free statement. Applications Solani Amylum is an excipient often used as filler in hard gelatin capsule formulations. This is commonly done in a blend with partly pregelatinised starch. In this application the necessary cohesiveness for plug formation at light tamping forces together with plug dispersion and drug release is readily achieved. Solani Amylum is also used as a disintegrant in tablets at levels of about 5% to 2% (Figure 2). When cooked up to a paste, Solani Amylum can be used as a binder in wet granulation applications. Figure 1 (bottom) shows the typical viscosity profile of cooked up Solani Amylum solution. Specification Moisture content < 2% ph Oxidising substances <.2% Sulphur dioxide < 5 ppm Iron < 1 ppm Total aerobic mesophilic count < 1 cfu/g Yeasts and moulds < 1 cfu/g E. coli (1g) Absent Salmonella (25g) Absent Label Declaration Solani Amylum Potato Starch USP-NF, Ph. Eur., JP. Packaging Multilayer 25kg white paper bag with polyethylene coating. Storage Store the product in well sealed bags, inside a cool and dry place. It is advised however, to keep the storage as short as possible to avoid gradually increasing moisture content. Viscosity (mpas) Disintegration time (sec) % 2% 4% 6% 8% 1% 12% 14% 16% Solids 5 kn 1 kn 15 kn Solani Amylum Prejel PA5 PH SuperTab11SD/1M (75:25) 1% SuperTab11SD/MCC12 (75:25) 1% Figure 1: Photomicrograph of granules of potato starch under polarised light (upper image) viscosity profile of native potato starch compared to fully pregelatinised potato starch (lower image). Figure 2: Disintegration time (in sec) of tablets compressed with 1% starch content with SuperTab 11SD/Pharmatose 1M and SuperTab 11SD/Pharmacel 12.

5 5 Prejel PA5 PH Fully pregelatinised potato starch Description Prejel PA5 PH is a cold water swelling fully pregelatinised potato starch in the form of a white, free flowing powder (figure 3). Prejel PA5 PH complies with USP NF and Ph. Eur. and JP monographs for pregelatinised starch. Prejel PA5 PH is also gluten free and can be provided with a GMOfree statement. Gelatinisation Gelatinisation is the collapse (disruption) of molecular orders within the starch granule where irreversible changes in properties occur such as granular swelling, crystallite melting, loss of birefringence, viscosity development, and starch solubilisation. The latter is especially important as the soluble content is high, which makes it very suitable as a binder. Applications Therefore, Prejel PA5 PH is widely used in oral solid dosage forms such as tablets. In wet granulation formulations Prejel PA5 PH can be added to the granulation liquid or to the dry blend. Prejel PA5 PH removes the costs of creating a starch paste while maintaining viscosity and providing extra flowability compared to Solani Amylum. As a binder used in wet granulation Prejel PA5 PH increases the hardness of a tablet and decreases its friability. Figure 4 shows how cost effective Prejel PA5 PH is as a binder compared to a synthetic polymer such as PVP. Specification Moisture content < 13% ph Sieve analysis >92% on 125 μm Oxidising substances negative Sulphur dioxide <.5% Iron (Fe) < 2ppm Total aerobic microbial count < 1 cfu/g Total yeasts and moulds < 1 cfu/g E. coli (1g) Absent Salmonella (25g) Absent Label Declaration Prejel PA5 PH Pregelatinised potato starch USP-NF, Ph. Eur., JP. Packaging Multilayer 25kg white paper bag with polyethylene coating. Storage Store well sealed bags, inside a cool and dry place. It is advised however, to keep the storage as short as possible to avoid gradually increasing moisture content. Prejel PA5 PH is especially suitable for dry addition in wet granulation because it reduces overwetting problems. crushing strength (N) Prejel PSS PVP Prejel PSS PVP Prejel PSS PVP Water.5% solution 2% dry addition 4% dry addition Figure 3: Photomicrograph of fully pregelatinised potato starch granules (Prejel PA 5 PH). Figure 4: Effect of different concentrations of binders (water, fully pregelatinised starch (Prejel), partially pregelatinised starch (PSS) and synthetic polymer (PVP)) in wet (5% binder solution, dry substance.5%) and dry state (1% water is used to moisten mass) using lactose (Pharmatose 2M) as filler.

6 6 SuperStarch 2 Partly pregelatinised starch Description SuperStarch 2 is a partly pregelatinised maize starch that integrates multiple functionalities including binder, diluent and disintegrant. SuperStarch 2 complies with all tests in major pharmacopoeia. The main application areas of SuperStarch 2 include tablets and capsules prepared by both direct compression/ blending and by wet granulation. SuperStarch 2 is produced by a mechanical gelatinisation process. Figure 6 shows SuperStarch 2 to be a combination of agglomerated particles and loose starch grains. Under polarised light (figure 7) the mixture of birefringent and nonbirefringent starch particles is seen confirming the partial pregelatinisation. SuperStarch 2 maintains low water activity compared to other common excipients (figure 8, left). Water sorption is completely reversible, as shown by the DVS cycle (figure 8, right). SuperStarch 2 contains both native and ruptured maize starch grains. Ruptured grains provide the soluble component, which is responsible for the binding properties in wet granulation. The native starch grains, a mixture of amylopectin and amylose (figure 5, approximately 73 and 27% respectively), are responsible for the disintegra ting properties of SuperStarch 2. Amylose Amylopectin Figure 6: Scanning electron photomicrograph of partially pregelatinised maize starch granules (SuperStarch 2) at 5X magnification. Figure 7: Photomicrograph (1X) of SuperStarch 2 under polarized light. Figure 5: Depicts the building blocks of maize starch as amylose (27%) and amylopectin (73%). Amylose provides the binding force while amylopectin helps in disintegration by swelling. Loss on drying (%) Water activity (-) Change in Mass (%) - Dry Competitor P-PGS SuperStarch 2 Microcrystalline cellulose DCP Anhydrous Anhydrous lactose Loss on drying (%) Water activity DCP Dihydrate Milled lactose % relative humidity Sorption 1 Desorption 1 Sorption 2 Desorption 2 Figure 8: Loss on drying and water activity of SuperStarch 2 versus other commonly used excipients (left) dynamic vapor sorption isotherm of SuperStarch 2 (double cycle).

7 7 Applications The combination of native and gelatinised starch particles allows SuperStarch 2 to act in a formulation as both binder as a disintegrant. In direct compression applications, SuperStarch 2 is best used in combination with other typical DC excipients, both soluble and non-soluble, such as direct compression lactose or microcrystalline cellulose (figures 9 and 1). A typical usage rate is in the range of 1-5 w/w %. In wet granulation, SuperStarch 2 acts both as a binder and a disintegrant. A typical usage rate is in the range of 5-25 w/w %. SuperStarch 2 is also a very effective excipient for simple direct blend formulations for encapsulation. It helps to form cohesive plugs that transfer cleanly into capsule shells, therefore helping to minimise dust formation during capsule filling. Specification SuperStarch 2 Min. Max. Cold water solubles (%) 1 2 Particle size specifications <53 um sieve (%) 25 1 <15 um sieve (%) 9 1 <425 um sieve (%) Residue on Ignition (%).5 Oxidising substances Negative ph Sulphur dioxide (ppm) 3 Loss on drying (%) 13 Typically measured and derived properties Typical poured density (g/ml).64 Typical tapped density (g/ml).8 Typical Hausner ratio 1.25 Typical Carr s Compressibility Index (%) 2 Typical Color Off white Packaging SuperStarch 2 is available in 25kg multilayer paper bags with a polyethylene inner liner. Storage Store well sealed bags, inside a cool and dry place. It is advised however, to keep the storage as short as possible to avoid gradually increasing moisture content. Disintegration time (sec) % drug released Tablet hardness (N) SD lactose/superstarch 2 (9:1) SD lactose/competitor P-PGS (9:1) MCC/SuperStarch 2 (5:5) MCC/Competitor P-PGS (5:5) Time (min) DC-SuperStarch 2 DC-Competitor P-PGS WG-SuperStarch 2 WG-Competitor P-PGS Figure 9: Disintegration time profile Vs. hardness for SuperStarch 2 in combination with MCC or spray-dried lactose in 25 mg placebo tablets. Figure 1: Comparative dissolution profile of medium dose (5mg) API in 2 mg wet granulated and directly compressed tablet composed of Superstarch 2 and Pharmacel 11.

8 Head Office Klever Strasse 187 P.O. Box Goch Germany T F pharma@dfepharma.com North America 61 South Paramus Road Suite 535 Paramus, NJ 7652 USA T F Japan Kudan Vigas Bldg 3F Kudan-Kita Chiyoda-Ku Tokyo 12-73, Japan T F Singapore 3 Temasek Avenue #11-1 Centennial Tower Singapore 3919 T F India Plot No. 148, Prestige Featherlite Tech Park 2nd Phase, EPIP Zone Whitefield, Bangalore 5666 India T F China Room 119, #1 Building No 2277 Zuchongzhi Road, 2123 Pudong Shanghai China T. +86 () F. +86 () Brazil Rua dos Canarios, 65 Vinhedo, Sao Paulo , Brazil DFE Pharma (#4/November 214) DMV-Fonterra Excipients GmbH & Co. KG - Warranty The details given here are merely intended for information purposes and are in no way legally binding. Consequently we accept no responsibility in the broadest sense of the word for damage that may result from applications based upon this information. Furthermore, this information does not constitute permission to infringe patent and licence rights.