GLYCOLYS

Transcription

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2 GLYCOLYS Looking for a superdisintegrant? The unique answer for many formulations ( summary Introduction page 2 GLYCOLYS general description page 3 Pharmacopoeial specifications and key properties page 3 An optimized production process page 4 Mechanism of action page 5 All modes of incorporation are possible... page 6 Regulatory page 7 An extended range page 7 Formulation support page 8 P A G E 1

3 ( introduction ( GLYCOLYS general description The role of a superdisintegrant is to make it possible for an oral dosage form to disintegrate very quickly. This is to facilitate the rapid dissolution - and hence bio-availability - of the drug. GLYCOLYS sodium starch glycolate (SSG) is a superdisintegrant. GLYCOLYS, the market benchmark is a long established product first developed in the 1970s and wellknown - and widely used - in the pharmaceutical industry. The decades of experience gained by Roquette with its GLYCOLYS range of SSGs have made the company a supplier of choice when help is needed to develop formulations. SEM picture of GLYCOLYS GLYCOLYS sodium starch glycolate (SSG) is a white-to-off-white, odourless, tasteless, free-flowing powder. It consists of oval to spherical granules, 30µm-100µm in diameter with some less spherical granules range in size between 10µm and 35µm ( pharmacopoeial specifications and key properties Sodium starch glycolate has a number of different names: sodium starch glycolate (BP and USP/NF); carboxymethylamylum natricum (EP); carboxymethyl starch (USP/NF); sodium carboxymethyl starch (USP/NF). CAS Registry number: [ ]- EINECS: The main advantage of GLYCOLYS is its versatility: Suitable for all oral dosage forms (tablets and capsules). Suitable for all manufacturing processes: - direct compression or wet granulation, - including high-shear granulation processes. Efficiency unaffected by lubricants. Different modes of incorporation are possible (intra and/or extra granularly; even mixed is possible). European Pharmacopoeia* USP / NF* Type A Type B Type C Type A Type B ph Loss on drying 10% 10% 7% 10% 10% Sodium % % % % % Sodium chloride 7% 7% 1% 7% 7% Sodium glycolate 2% 2% 2% 2% 2% Heavy metals 20ppm 20ppm 20ppm 20ppm 20ppm Iron 20ppm 20ppm 20ppm 20ppm 20ppm *According to European Pharmacopoeia 5.4 and USP29/NF24 Second Ed. Bulk density: 0.756g/cm 3 Tapped density: 0.945g/cm 3 Specific surface area: 0.24m 2 /g Swelling capacity: in water, sodium starch glycolate swells to up to 300 times its original volume. Dynamic viscosity: < 200mPa.s for a 4% w/v aqueous dispersion. Solubility: sparingly soluble in ethanol (95%); practically insoluble in water. (Indicative values) P A G E 2 P A G E 3

4 ( an optimized production process for ideal disintegration properties ( mechanism of action Potato starch is the preferred raw material for GLYCOLYS. Its granules are relatively large (10µm - 100µm). To avoid viscosity development during disintegration process that would delay drug dissolution, cross-linking is performed on the potato starch. GLYCOLYS production process Sodium trimetaphosphate Sodium monochloroacetate NaOH Citric acid Ethanol - Water Potato starch Cross-linking Cross-linked potato starch Carboxymethylation Neutralization Washings, separation Drying Packaging GLYCOLYS sodium starch glycolate For a maximum speed of disintegration, starch ability to swell is significantly increased by rendering it more hydrophilic through carboxymethylation. For a maximum purity in the GLYCOLYS products, neutralization and washings are performed. Swelling power of different disintegrants Swelling power The mechanism of action depends on the nature of the superdisintegrant. However, swelling of the superdisintegrant particle plays a major role in all cases. The swelling power of disintegrants varies greatly from one disintegrant to another. A chain reaction involving water absorption and disruption into a solid dosage form has been proposed by Bolhuis (1982) as the mechanism of action for strongly-swelling superdisintegrants like GLYCOLYS. The mechanism explains why sodium starch glycolate is not sensitive to lubricants. Because the potato starch granule is very large, the lubricant film is unable to cover its entire surface. Water therefore reaches the starch granule at the surface of the tablet, which then swells and starts to disintegrate. Scientific studies have clearly demonstrated that lubrication has no effect on an SSG like GLYCOLYS (Bolhuis et al, 1981; Lerk et al, 1982) Strongly swelling superdisintegrants Moderately swelling disintegrants Lightly swelling disintegrants Sodium starch glycolate GLYCOLYS Croscarmellose sodium Crospovidone Potato starch Microcrystalline cellulose Mechanism of action of strongly swelling superdisintegrants Water absorption of disintegrant particles at the outside of the tablet Swelling of disintegrant particles Disintegration of tablet surface structure Water penetration into the opened tablet structure Chain reaction of absorption and disruption Disintegration The mechanism also explains the superiority in hard gelatine capsules of sodium starch glycolates over other superdisintegrants. For instance, because croscarmellose s fibres retain their integrity it dissolves only partially, thus forming a viscous medium that hinders drug dissolution (Hannula et al, 1989). By contrast, GLYCOLYS sodium starch glycolate maintains granule integrity during swelling, viscosity is not altered and the drug component dissolves normally. Crospovidone is also inferior to SSG: much affected by compression forces, it loses its efficiency when a plug is formed, making it unsuitable for capsules. P A G E 4 P A G E 5

5 ( all modes of incorporation are possible: intragranularly, extragranularly or mixed GLYCOLYS can be incorporated into a formula in accordance with three commonly occurring pharmaceutical industry processes: Internal phase: the SSG can be used as a disintegrant as well as a binding enhancer for granulation. External phase: the SSG is added with other ingredients at the end of blending just before the lubricant. This is the case when formulating a direct compression blend. Mixed incorporation process (i.e. intra- and extragranular): an optimized incorporation process producing fast and efficient disintegration and dissolution, while improving the general characteristics of the dosage form (hardness, friability ). Effect of GLYCOLYS mode of incorporation on tablet disintegration time 2500 In trials carried out with mannitol PEARLITOL -based tablets containing 5% GLYCOLYS, tablet disintegration time was dramatically reduced, irrespective of the mode of incorporation. Hardness and friability were similar to the control tablets. It will be noted that the best results obtained with GLYCOLYS occur when the superdisintegrant is used extragranularly. When the SSG is totally incorporated intragranularly, the disintegration kinetic is reduced due to the slow disruption mechanism in the tablet surface structure. A mixed process also reduces GLYCOLYS efficiency. However, in all cases the addition of GLYCOLYS reduces disintegration times relative to the control. In specific cases using wet granulation, GLYCOLYS LV (low viscosity grade) is more appropriate, resulting in even shorter disintegration times (see separate GLYCOLYS LV document). GLYCOLYS LV For wet granulation and high shear processes GLYCOLYS Low ph ( regulatory Roquette s entire GLYCOLYS SSG range complies with EP and USP/NF Pharmacopoeias. ( an extended range GLYCOLYS For ph-sensitive drugs Multipurpose For all other requirements Disintegration time (s) Control Intragranularly Extragranularly 50 intra/50 extra P A G E 6 P A G E 7

6 ( formulation support Roquette has very wide experience of GLYCOLYS sodium starch glycolate, not least in oral solid dosage form formulations. We are dedicated to providing you with the technical support and help you may need to develop your own formulations. Download examples of formulations at: Alternatively, fill in our Formulation Assistance Request and we will help you choose the excipients that will give you the keys you need for your formulation trials. Through still closer collaboration with you we can also arrive at a comprehensive formulation for your product; we can also provide you with placebos or prototypes. Literature Bolhuis et al, 1982, Acta Pharm. Technologica 28(2), Bolhuis et al, 1981, Journal of Pharm. Sciences 70(12), Lerk et al, 1982, Pharm. Acta Helv. 57, Hannula et al, 1989, Acta Pharm. Fennica 98, The information contained in this document is to the best of our knowledge true and accurate but all instructions, recommendations or suggestions are made without any guarantee. Since the conditions of use are beyond our control, we disclaim any liability for loss and/or damage suffered from use of these data or suggestions. Furthermore, no liability is accepted if use of any product in accordance with these data or suggestions infringes any patent. No part of this document may be reproduced by any process without our prior written permission. Registered trademarks of Roquette Frères Roquette Frères S.A. - 03/2010 P A G E 8

7 GLYCOLYS at a glance Suitable for tablets and capsules Low incorporation level: 2-5% in tablets 4-8% in capsules Usable in internal and external phases, or mixed Not sensitive to lubricant Not influenced by compression force Low hygroscopicity Chemically stable In use as superdisintegrant for more than 30 years Can be sourced reliably worldwide