Pharmaceutical Technology: Controlled Drug Release, Volume 2

More documents

Recommendations

Info

13 A comparison of dissolution properties from matrix tablets prepared from microcapsules and mixtures containing phenobarbitone and poly(DL-lactic acid) Biljana Oraceska, Reza Ul Jalil and J.R.Nixon Chelsea Department of Pharmacy, King’s College London, Manresa Road, London SW3 6LX, UK SUMMARY Microcapsules for use in the preparation of sustained release formulations have been under investigation for a number of years without any great success. There is an initially rapid release, due to the porosity of the wall coupled with the effect of wall saturation, which builds up during long storage. Compression has provided formulations with better sustained release characteristics. The materials traditionally used for the walls have been non-biodegradable and this meant that only the oral route has been available. The present study investigates a biodegradable polymer, poly(DL-lactic acid) (DL-PLA), as the microcapsule wall. Tablets of microcapsules prepared with this method should be capable of use as subcutaneous implants. Three different compression forces, 2, 5 and 10 kN, were used, with core:wall ratios of 1:1 and 2:1. For comparison, the same proportions of drug and coating polymer were compressed without prior microencapsulation. The release of the drug phenobarbitone (PB) from tablets prepared using simple mixtures of DL- PLA and PB, as well as from the corresponding tablets from microencapsulated PB, is reported. These results are compared with release from the original microcapsules. INTRODUCTION Oral administration is a relatively safe route for sustained action drug delivery. Oral delivery allows the use of either tablets or capsules [1]. A wide range of techniques is available for their preparation.
142 CH. 13] A COMPARISON OF DISSOLUTION PROPERTIES The drug may be incorporated in a slowly eroding matrix of waxy materials, embedded in a plastic matrix, complexed with anion exchange resins or incorporated in a water-insoluble hydrophilic matrix. <strong>Drug</strong> release from these systems occurs by several mechanisms; diffusion, dissolution, ionic exchange or osmotic pressure [1,2], depending on the type of polymeric excipient present and the formulation used. In most cases the polymeric excipient is the principal component of the sustained release formulations which retards drug release from the dosage form. Many hydrophilic, hydrophobic or pH-sensitive polymers have been used in oral dosage forms [3]. Poly(lactic acid) (PLA) was first suggested by Kulkarni et al. [4] as a suitable biodegradable polymer for surgical sutures and implant material, and Yolles et al. [5] made use of it as an erodible implant for the controlled release of naltrexone, a narcotic antagonist. Beck et al. [6,7] reported the preparation of longacting injectable microcapsules containing a contraceptive steroid using this polymer. During the past 15 years many workers have utilized this polymer. During the past 15 years many workers have utilized this polymer to fabricate a wide range of drugs in the form of implants, microcapsules, microspheres, nanoparticles and pseudolattices [8–13]. Poly(lactide) can be synthesized from two optically isomeric forms of lactic acid: L-lactic acid [14]. The polymers prepared from these isomers, L-PLA and DL-PLA, vary considerably with respect to their physical properties (crystallinity, glass transition temperatures, water uptake, etc.) which could be crucial in a diffusion-controlled drug delivery system. <strong>Drug</strong> diffusion occurs almost exclusively through the amorphous region of the polymer, so the crystalline polymer can be regarded as providing a heterogeneous medium for diffusion [15]. As L-PLA is highly crystalline, whereas DL-PLA is almost exclusively amorphous [16], diffusion through the latter should be more rapid and also more amenable to modification. Although much work has been reported on the polymers, the use of PLA in sustained release tablet formulations is not well documented. However, Coffin et al. [17] reported the preparation of pseudolattices from poly (DLlactide) which they subsequently used to prepare sustained release theophylline tablets. In the present study we report the release of phenobarbitone (PB) from tablets derived from simple mixtures of DL-PLA and PB as well as from microencapsulated PB, and the effect of the compressive force. These results are compared with release from the original microcapsules. EXPERIMENTAL Materials Poly(DL-lactic acid) (Boehringer) and phenobarbitone (Sigma) were used. All other materials were of standard reagent grade purity. Preparation of microcapsules Poly(DL-lactic acid) and phenobarbitone were dissolved in acetonitrile at 55°C and added to a liquid paraffin-Span 40 (50:1) mixture at the same temperature. The mixture was stirred at 2000
Page 2 and 3:
PHARMACEUTICAL TECHNOLOGY Controlle
Page 4 and 5:
3 TABLET MACHINE INSTRUMENTATION IN
Page 6 and 7:
First published in 1991 by ELLIS HO
Page 8 and 9:
7 10 Controlled delivery of theophy
Page 10:
Slow and steady wins the race Poems
Page 14 and 15:
1 Influence of drug solubility in t
Page 16 and 17:
CH. 1] INFLUENCE OF DRUG SOLUBILITY
Page 18 and 19:
Page 20 and 21:
Page 22:
Page 25 and 26:
24 MATRIX FORMULATIONS [CH. 2 MATER
Page 27 and 28:
26 MATRIX FORMULATIONS [CH. 2 Fig.
Page 29 and 30:
28 MATRIX FORMULATIONS [CH. 2 Table
Page 31 and 32:
30 MATRIX FORMULATIONS [CH. 2 The e
Page 33 and 34:
Page 35 and 36:
34 CH. 3] THE FORMULATION OF SUSTAI
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 44 and 45:
4 Statistical optimization of a con
Page 46 and 47:
MATRIX FORMULATIONS [CH. 4 45 (4) G
Page 48 and 49:
MATRIX FORMULATIONS [CH. 4 47 Fig.
Page 50 and 51:
Columns 1-4 lead to the matrix of e
Page 52 and 53:
MATRIX FORMULATIONS [CH. 4 51 Table
Page 54 and 55:
MATRIX FORMULATIONS [CH. 4 53 Fig.
Page 56:
Fig. 5—Linearization of the relea
Page 59 and 60:
58 MATRIX FORMULATIONS [CH. 5 Pevik
Page 61 and 62:
60 MATRIX FORMULATIONS [CH. 5 The d
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 72 and 73:
6 Controlled release matrix tablets
Page 74 and 75:
CH. 6] CONTROLLED RELEASE MATRIX TA
Page 76 and 77:
Page 78 and 79:
Page 80 and 81:
7 A new ibuprofen pulsed release or
Page 82 and 83:
CH. 7] A NEW IBUPROFEN PULSED RELEA
Page 84 and 85:
Page 86 and 87:
Page 88:
Page 91 and 92: 90 CH. 8] TOPICAL RELEASE AND PERME
Page 101 and 102: 100
Page 103 and 104: 102
Page 105 and 106: 104 MULTIPARTICULATES [CH. 9 parace
Page 107 and 108: 106 MULTIPARTICULATES [CH. 9 (a) th
Page 109 and 110: 108 MULTIPARTICULATES [CH. 9 Fig. 2
Page 117 and 118: 116
Page 119 and 120: 118 CH. 10] CONTROLLED DELIVERY OF
Page 127 and 128: 126 CH. 11] THE EFFECT OF FOOD ON G
Page 129 and 130: 128 CH. 11] THE EFFECT OF FOOD ON G
Page 131 and 132: 130
Page 133 and 134: 132 CH. 12] BIODEGRADABLE POLYMERS
Page 141: 140
Page 145 and 146: 144 CH. 13] A COMPARISON OF DISSOLU
Page 153 and 154: 152
Page 155 and 156: 154
Page 157 and 158: 156 OPHTHALMIC FORMULATION [CH. 14
Page 163 and 164: 162 CH. 15] A SUSTAINED RELEASE OPH
Page 171 and 172: 170
Page 173 and 174: 172 IMPLANTS [CH. 16 The purpose of
Page 175 and 176: 174 IMPLANTS [CH. 16 times with 5 m
Page 177 and 178: 176 IMPLANTS [CH. 16 noted that the
Page 179 and 180: 178 IMPLANTS [CH. 16 Fig. 1—The e
Page 181 and 182: 180 IMPLANTS [CH. 16 Table 3—Tobr
Page 183 and 184: 182
Page 185 and 186: 184 CH. 17] SILICON MATRIX SYSTEMS
Page 193 and 194:
192
Page 195 and 196:
194 INDEX dry granulation, 43 elect
show all

Pharmaceutical Technology: Controlled Drug Release, Volume 2

Create successful ePaper yourself

Delete template?

Save as template?