Pharmaceutical Technology: Controlled Drug Release, Volume 2

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1 Influence of drug solubility in the formulation of hydrophilic matrices B.Huet de Barochez, J.S.Julien, F.Lapeyre, S.Horvath and A.Cuiné Ardix, 25 rue E.Vignat, F-45000 Orléans, France INTRODUCTION Sustained release dosage forms are a convenient means to obtain a reduction in daily administration of drugs with fast absorption and/or elimination. In this study three different drugs are compared: one is slightly water soluble, and two are highly water soluble (Table 1). Production of hydrophilic matrices is a well-known technology, by direct compression as well as by wet granulation [1,2]. A lot of research has been done and the literature on this subject is plentiful. Different polymers may be used to control the diffusion of the drug. Among them, hydroxypropylmethylcellulose (HPMC) seems most employed [3–5]. Table 1—<strong>Drug</strong> characteristics MATERIALS The following ingredients were used for the preparation of hydrophilic matrices: calcium hydrogen phosphate dihydrate, (SPCI, La Plaine Saint Denis), calcium hydrogen phosphate for direct compression (Emcompress, SPCI), lactose 150 mesh (Sucre de Lait, Sains-du-Nord),
14 MATRIX FORMULATIONS [CH. 1 lactose Fast Flo (SEPPIC, Paris), polyvinylpyrrolidone (PVP) (Luviscol K30, BASF, Levallois), HPMC (Methocel K4M and E4M CR, Colorcon, Bougival or Metolose 60SH4000 and 90SH4000, SEPPIC), hydroxyethylcellulose (HEC) (Natrosol, Aqualon, Rueil-Malmaison), magnesium stearate (Stéarinerie Dubois, Paris) and colloidal silicon dioxide (Aerosil 200, Degussa, Neuilly sur Seine). Different grades of Methocel and Metolose are supplied, with nominal viscosities of 4000 mPa s (measured with a Brookfield viscometer on a 2% w/v solution). Methocel 4M types E and K are different in their hydration rates, type K being the quickest. Metoloses SH4000 differ in their gel temperature. Grades 60 and 90 were used. Another polymer of 4000 mPa s viscosity was used: hydroxyethylcellulose, in order to observe effects on the dissolution rate. FORMULATION, PREPARATION AND TESTS <strong>Drug</strong> A With drug A, HPMC was used at different concentrations, from 25.3% to 41.0% (Table 2). Five 1 kg batches were prepared using direct compression. Lactose and Emcompress were mixed together, using a rotary mixer, and then drug was incorporated by trituration. HPMC was mixed with Aerosil 200 in the same mixer, blended with the first mix, mixed and lubricated with magnesium stearate. Compression was conducted on a MR12 rotary press (Frogerais, Ivry sur Seine) equipped with 7 mm diameter punches with a 5 mm concavity. Compression force was adjusted to obtain tablets with a hardness of about 7 daN. Table 2—DC tablet formulae (mg) Two batches were prepared by wet granulation, one with lactose as a diluent (Table 3), the other with calcium hydrogen phosphate. Diluent, drug and PVP were mixed together at 200 rev min −1 in a high speed granulator dryer (Turbo-sphère) TS10 (Moritz, Chatou). The mixture was granulated at the same speed for 5 min, using a 30–70 water-alcohol solution. After drying (60°C under vacuum), the product was sized with an oscillating granulator, blended with HPMC in a rotary mixer, then lubricated with Aerosil and magnesium stearate in the same mixer. Compression was conducted on a rotary press (MR12) equipped with 8 mm diameter punches with 7 mm concavity.
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6 Controlled release matrix tablets
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CH. 6] CONTROLLED RELEASE MATRIX TA
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7 A new ibuprofen pulsed release or
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CH. 7] A NEW IBUPROFEN PULSED RELEA
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108 MULTIPARTICULATES [CH. 9 Fig. 2
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118 CH. 10] CONTROLLED DELIVERY OF
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126 CH. 11] THE EFFECT OF FOOD ON G
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128 CH. 11] THE EFFECT OF FOOD ON G
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132 CH. 12] BIODEGRADABLE POLYMERS
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142 CH. 13] A COMPARISON OF DISSOLU
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156 OPHTHALMIC FORMULATION [CH. 14
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162 CH. 15] A SUSTAINED RELEASE OPH
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172 IMPLANTS [CH. 16 The purpose of
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174 IMPLANTS [CH. 16 times with 5 m
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176 IMPLANTS [CH. 16 noted that the
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180 IMPLANTS [CH. 16 Table 3—Tobr
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184 CH. 17] SILICON MATRIX SYSTEMS
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194 INDEX dry granulation, 43 elect
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Pharmaceutical Technology: Controlled Drug Release, Volume 2

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