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L1.9 Multifunctional excipients for direct compression of tablets
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L1.9 MULTIFUNCTIONAL EXCIPIENTS DIRECT COMPRESSION OF TABLETS P Paronen Dept. of Pharmaceutics, Univ. of Kuopio, POB 1627, FIN-7021 1 Kuopio
Lectures
FOR
Tableting properties as well as pH-dependent drug release from direct compression tablets consisted of starch esters as excipients were evaluated. Barley starch was esterified for preparing starch acetate, succlnate, proplonate or hexanoate. Only starch acetates possessed suitable direct compression properties. Starch acetates were relatively easy flowing. The increase in substitution degree increased the mechanical strength of the tablets. The energy consumption was well comparable to the best commercial direct compression exclpients. The materials with the substitution degree of about 0.20.8, 0.6-2.0, 1.8-3.0 were suitable to be used as disintegrants, filler/binders and controlled release matrice former% respectively. By optimizing the substitution degree of stach acetate, or the ratios of amounts of differently substituted starch acetates In the powder mixture enabled us to formulate widely different direct compression tablets. All the starch acetates were noticed to undergo plastic deformation under compression. With higher acetate content the material formed increasingly intact continuous matrice structure. Thus the release profile of a model drug substance, propranolol hydrochloride, was widely possible to adjust. Further starch succinate was added as a pHdependent polymer excipient into the theophylline anhydrate tablets consisted of starch acetate as matrice former. Clear pH-dependence was noticed in theophylline release. Burst effect in drug release was minimized by increasing the compressional force. Thus tablets with pH-dependent drug release properties and enough firm structure were able to be prepared using the direct compression method. As a conclusion, starch acetates seemed to be promising novel excipient candidates for direct compression of tablets and starch succinate an interesting novel pH-dependent excipient for tableting. Financial support - Technology Development Center, TEKES, Finland and Primalco Oy, Polymers, Rajamaki, Finland.
L1.10 NEW FORMULATIONS OF METHACRYLATE COPOLYMERS FOR IMPROVED COATING TECHNOLOGY - KLehmacm Research and Development, Pharma Polymers, ROHM GmbH, D-64293 Darmstadt
Methacrylic acid copolymers (USP types A,B and C) as effective enteric coatings exhibit distinct solubility in the intestine dependent on content of carboxylic groups and ester component. Ammonio methacrylate copolymers (USP types A and B) are hydrophilic, permeable coatings. All products are available as aqueous dispersions and specific release profiles can be developed by polymer blending and selected excipients. Coated particles as multi unit dosage forms are most reliable; they can be compressed to disintegrating tablets without severe damage, if films are extensible to min. 75Ohelongation at break Such flexible enteric films are now available from new polymers containing only IO- 20% of methacrylic acid (MA) and methyl-acrylate (MeA) as a wmonotner. They are produced by emulsion polymerisation and can be extruded to solid forms as granules, films, capsules and others. MeA is responsible for the high effectiveness of the carboxylic groups. A copolymer MA-MeA= dissolves at pH 6,O. When methylmethacrylate (MMA) was used as a third component, the polymer films dissolved at higher pH. A polymer composed of MA-MeA-MMA = 1O-65-25 (Prep.41 10 0) dissolved at pH 7. Glass transition temperature is around 50°C much lower compared to other enteric coatings. Flexibility of films increases considerably with low amonts of plasticizer: Elongation of break is lOOoh with 6% TEC and 300°h with 10% TEC. Temperature stability is above 200°C. Films and special dosage forms can be prepared not only by spraying or casting of their aqueous dispersions or organic solutions but also by hotmelt coating, extrusion and molding processes. The new polymer was successfully applied in coating of bisacodyl, paracetamol, naproxen tablets and bisawdyl, phenylpropanolamine and prednisolone pellets. Lehmann K. Petereit H-U.and Dreher 0. (1993) Pharm.lnd.55,615-618 and 940-947
L1.9 MULTIFUNCTIONAL EXCIPIENTS DIRECT COMPRESSION OF TABLETS P Paronen Dept. of Pharmaceutics, Univ. of Kuopio, POB 1627, FIN-7021 1 Kuopio
Lectures
FOR
Tableting properties as well as pH-dependent drug release from direct compression tablets consisted of starch esters as excipients were evaluated. Barley starch was esterified for preparing starch acetate, succlnate, proplonate or hexanoate. Only starch acetates possessed suitable direct compression properties. Starch acetates were relatively easy flowing. The increase in substitution degree increased the mechanical strength of the tablets. The energy consumption was well comparable to the best commercial direct compression exclpients. The materials with the substitution degree of about 0.20.8, 0.6-2.0, 1.8-3.0 were suitable to be used as disintegrants, filler/binders and controlled release matrice former% respectively. By optimizing the substitution degree of stach acetate, or the ratios of amounts of differently substituted starch acetates In the powder mixture enabled us to formulate widely different direct compression tablets. All the starch acetates were noticed to undergo plastic deformation under compression. With higher acetate content the material formed increasingly intact continuous matrice structure. Thus the release profile of a model drug substance, propranolol hydrochloride, was widely possible to adjust. Further starch succinate was added as a pHdependent polymer excipient into the theophylline anhydrate tablets consisted of starch acetate as matrice former. Clear pH-dependence was noticed in theophylline release. Burst effect in drug release was minimized by increasing the compressional force. Thus tablets with pH-dependent drug release properties and enough firm structure were able to be prepared using the direct compression method. As a conclusion, starch acetates seemed to be promising novel excipient candidates for direct compression of tablets and starch succinate an interesting novel pH-dependent excipient for tableting. Financial support - Technology Development Center, TEKES, Finland and Primalco Oy, Polymers, Rajamaki, Finland.
L1.10 NEW FORMULATIONS OF METHACRYLATE COPOLYMERS FOR IMPROVED COATING TECHNOLOGY - KLehmacm Research and Development, Pharma Polymers, ROHM GmbH, D-64293 Darmstadt
Methacrylic acid copolymers (USP types A,B and C) as effective enteric coatings exhibit distinct solubility in the intestine dependent on content of carboxylic groups and ester component. Ammonio methacrylate copolymers (USP types A and B) are hydrophilic, permeable coatings. All products are available as aqueous dispersions and specific release profiles can be developed by polymer blending and selected excipients. Coated particles as multi unit dosage forms are most reliable; they can be compressed to disintegrating tablets without severe damage, if films are extensible to min. 75Ohelongation at break Such flexible enteric films are now available from new polymers containing only IO- 20% of methacrylic acid (MA) and methyl-acrylate (MeA) as a wmonotner. They are produced by emulsion polymerisation and can be extruded to solid forms as granules, films, capsules and others. MeA is responsible for the high effectiveness of the carboxylic groups. A copolymer MA-MeA= dissolves at pH 6,O. When methylmethacrylate (MMA) was used as a third component, the polymer films dissolved at higher pH. A polymer composed of MA-MeA-MMA = 1O-65-25 (Prep.41 10 0) dissolved at pH 7. Glass transition temperature is around 50°C much lower compared to other enteric coatings. Flexibility of films increases considerably with low amonts of plasticizer: Elongation of break is lOOoh with 6% TEC and 300°h with 10% TEC. Temperature stability is above 200°C. Films and special dosage forms can be prepared not only by spraying or casting of their aqueous dispersions or organic solutions but also by hotmelt coating, extrusion and molding processes. The new polymer was successfully applied in coating of bisacodyl, paracetamol, naproxen tablets and bisawdyl, phenylpropanolamine and prednisolone pellets. Lehmann K. Petereit H-U.and Dreher 0. (1993) Pharm.lnd.55,615-618 and 940-947