Relation between polymer composition solvent and nonsolvent

Mechanism of coacervate formation in a non-aqueous system has been investigated by Ruiz etal. (1989). Microcapsules of poly (DL-lactic acid-co-glycolic acid) were prepared by dissolving the polymer in methylene chloride and then adding various quantities of silicone oil to effect phase separation. The phase separation phenomenon was observed by taking photomicro graphs after increasing quantities of the incompatible polymer were added. At the first step when the amount of phase inducer is low...

Melt pelletization

High energy input, a controlled amount of liquid phase, and a uniform liquid distribution, are the prerequisites to produce pellets by wet granulation accordingly, melt granulation in high shear mixers is likely to be appropriate for pelletization of powders insofar as the mixer can supply the required energy input. Schaefer etal. (1992a,b,c) have demonstrated that commercial qualities of calcium hydrogen phosphate and lactose can be pelletized with PEGs in a Pellmix 10 high shear mixer. The...

Mobile liquid bonding strength

The tensile strength of agglomerates with localized bondings can be approximated by the following equation (Rumpf, 1962) in which a, is the mean tensile strength per unit section area, e is the void fraction of the agglomerate, d is the diameter of the particles, and H is the tensile strength of a single bond. The equation was derived by considering a particle assembly of monosized spheres. An approximate solution of equation 1 for agglomerates in the pendular state was given by Pietsch (1969)...

Definitions

The earliest known appearance of the word, phase, was in 1812 (Onions, 1933). An appropriate definition of the word for this chapter is 'a homogeneous, physically distinct, and mechanically separable portion of matter that is present in a non-homogeneous, physical-chemical system and that may be a single compound or a mixture,' (Gove, 1963). Phase separation is a broad term that may be applied to various processes such as the formation of a solid or liquid phase from a solution. Examples are...

Growth kinetics

Kapur (1978) presented an extensive review of the kinetics of wet granulation processes. On the supposition that the growth is controlled by a single mechanism, mathematical models for the changes in size and size distribution were presented. Such models are highly useful in analysing agglomeration processes, especially in the understanding of the agglomeration mechanisms and the resulting size distributions of a particular process. If, in the course of the agglomeration, successive granule...

Shellac

Sheorey etal. (1991) encapsulated sulfadiazine with shellac, using solvent evaporation. The drug was dispersed in a solution of shellac dissolved in isobutanol which has a higher boiling point than water. This suspension was then added slowly in a thin stream into a freshly prepared aqueous ben-tonite solution at 70 C. Phase separation occurred and the drug was coated upon evaporation of the solvent. The microcapsules were filtered, washed with water and dried. While a dry product could be...

Process and product variables

Schaefer etal. (1990b) investigated melt granulation in a 10-1 Baker Perkins high shear mixer using polyethylene glycol (PEG) 3000 and 6000. The starting materials were calcium hydrogen phosphate (dgw 23 m) and lactose (dgw 68 fim) of a quality identical to that used in a study on wet granulation in the same mixer (Schaefer etal., 1990a). Direct comparisons between wet and melt granulation can therefore be made. A conclusion of the work, which agrees well with the conclusions made by Kinget and...

A single wallforming polymer soluble in an organic liquid

Addition of a miscible liquid, a non-solvent for the polymer Wall polymer. Wall-forming polymers include acrylates, cellulose acetate, cellulose acetate butyrate, ethylcellulose, poly(lactic acid), poly(lactic-co- glycolide), polystyrene, polyvinyl acetate, polyvinyl chloride and other polymers (Fong, 1988). Control of agglomeration. Fong (1988) described a number of patents regarding agglomeration. Agglomeration of poly(lactic acid) microcapsules prepared from a dispersion of drug particles in...

Relationships Between Properties

All the properties described above are interrelated with specific ratios between them associated with second-order characteristics such as brittleness, ductility, plasticity and toughness. In this section a number of relationships are reviewed and their usefulness examined. Of specific interest is the semiempirical equation derived by Marsh (1964) while studying Vickers indentation From this relationship (Fig. 19) and a knowledge of the materials studied it is possible to show first that if E...

Cellulose acetate butyrate

Sprockel and Prapaitrakul (1990) encapsulated paracetamol with the polymer cellulose acetate butyrate by employing three different emulsion techniques. In the emulsion solvent evaporation method (ESE) the drug was dispersed in the polymer solution using acetone as the solvent. This phase was then emulsified in a liquid paraffin solution containing 1 sorbitan monooleate and stirred at 1400 r.p.m. at room temperature until the solvent had evaporated. The microspheres were collected, washed with...

Wallforming polymers soluble in water

Wall polymers include acacia, alginate, carboxymethyl-cellulose, gelatin, polyethylene glycol, poly (vinyl alcohol), albumin, car-bupol and pectin. Appropriate polymers may be used singly or in pairs as described below. Cores - water-soluble. In general, water-soluble solids or liquids are not encapsulated to a great extent when water-soluble polymers are used because the core will be distributed between the aqueous polymer-rich phase and the aqueous polymer-poor phase. There are,...

Gelatin

Phares and Sperandio (1964) showed that a number of insoluble particles, liquids and solids, could be encapsulated with gelatin using sodium sulfate as the coacervation-inducing agent. A phase diagram for the system gelatin, water and sodium sulfate was prepared to show the region of encapsulation. As a result of the preparation of phase diagrams (Nixon etal., 1966), suitable compositions within the coacervate region were selected for preparing microcapsules. Subsequently, an improved method...

References

B. (1986). Drug Dev. Ind. Pharm. 12, 471-487. Aulton, M. E. and Banks, M. (1981). Int. J. Pharm. Tech. & Prod. Mfr. 2 (4), 24-29. Bier, H.-P., Leuenberger, H. and Sucker, H. B. (1979). Pharm. Ind. 41, 375-380. Bowden, F. P. and Tabor, D. (1964). The Friction and Lubrication of Solids. Part , pp. 299-306. Oxford University Press, Oxford. Capes, C. E. (1980). Particle Size Enlargement. Elsevier, Amsterdam. Capes, C. E., Germain, R. J. and Coleman, R. D. (1977)....

Polylacticcoglycolic acid

Lewis and Tice (1984) encapsulated several steroids, namely norethisterone, norgestimate, testosterone propionate, oestradiol benzoate, progesterone and levonorgestrel, with poIy(DL-lactide-co-glycolide) using a solvent evaporation method. The quality of the microcapsules was determined by scanning electron microscopy and rate of release. Thyrotropin-releasing hormones or analogues have been encapsulated with lactic acid-glycolic acid copolymer by means of an emulsion (Heya etal., 1988). The...

Ill A single wallforming polymer soluble in an organic liquid

Addition of a miscible liquid, a non-solvent for the polymer In this process, the polymer is dissolved in an appropriate organic solvent, then a non-solvent, which is miscible with the polymer solvent, is used to induce phase separation. The non-solvent may be organic or an aqueous liquid (Kondo, 1979a). Frequently, low polymer concentrations are used, along with gradual phase separation to promote appropriate encapsulation. This permits the polymer solution to deposit onto the core and at the...

Melt Granulation Process and equipment

Melt granulation - also called thermoplastic granulation - is an agglomeration process based upon the use of a binder material which is solid at room temperature and softens or melts at slightly elevated temperatures, usually above 50-60 C. When melted, the action of the liquid binder is similar to the action of a binder solution in a wet granulation process. The binders normally used for melt granulation are polyethylene glycols (Rubinstein, 1976 Ford and Rubinstein, 1980 Pataki etal., 1983...

Acrylates

Hydrophobic compounds have been encapsulated with 2-diethylaminoethyl methacrylate-methacrylic acid-styrene copolymer latex by Ushiyama (1979). For example, castor oil was emulsified in water containing an anionic surfactant, Emal A, to a particle size of 30-50 m. The pH was adjusted to about 9 and the polymer added, which has an isoelectric point of 7.2, and the pH adjusted to 9-10 with NaOH. After acidifying to a pH of 5-5.5 to form the capsules, the product was spray dried. Donbrow etal....

Pelletization by wet granulation

Pelletization is a size enlargement process by which fine powders are converted into uniformly sized granules, preferably of spherical shape. Pellets for pharmaceutical purposes range in size, typically, from 0.5 to 1.5 mm, and are produced primarily for oral dosage forms with gastro-resistant or prolonged release properties. As drug delivery systems become more sophisticated, the role of pellets in the design and development of dosage forms is increasing. Methods commonly used for...

Principles Of Ocular Pharmacokinetics Topical ocular drug administration

A schematic and simplified presentation of ocular pharmacokinetics related to topical ocular administration is shown in Fig. 1. REMOVAL BY DRAINAGE, BLINKING, INDUCED LACRIMATION, AND TEAR TURNOVER fig. 1 Schematic presentation of ocular pharmacokinetics related to topical ocular drug administration. When eyedrops are administered to the ocular surface the solution mixes with the tear fluid. After administration the extra solution volume rapidly flows from the eye (Chrai etal., 1973, 1974)...

Gelatinacacia

Luzzi and Gerraughty (1964) used gelatin and acacia to encapsulate various oily liquids. After effecting coacervation, first at pH 6.5 at 50 C, then at pH 4.5, formaldehyde was added and the mixture cooled to 10 C and then the pH was adjusted to 9.0 to rigidize the coacervate droplets. The permeability, as shown by extraction studies of the gelatin acacia shell, is not affected by oils with different saponification values ranging from 2.5 to 12. However, the amount of oil extracted increases as...

Polyvinyl alcohol

Coacervates of polyvinyl alcohol have been prepared using colloidal silica as the core material Iler, 1973, 1974 . The coacervate was prepared from a dilute aqueous solution of the polymer and colloidal silica at pH 10. The pH was lowered to 2.6 with HC1 and deaerated with a mixture of dodecyl alcohol and propyl alcohol, boiled in a vacuum and cooled to 25 C to form the coacervate. The maximum yield of coacervate was obtained when the ratio of colloidal silica to polymer in the coacervate was...

Comparison between mixergranuiators

Figure 19 shows the effect of moisture content upon mean granule size when granulating calcium hydrogen phosphate with a PVP-PVA copolymer solution. With the Fielder mixer, considerably less liquid is required to achieve a certain granule size than with the Lodige mixer. In addition, the impeller rotation speed affects the liquid requirements. Examination of the porosity changes during the process shows that the Fielder mixer is more efficient at densifying the agglomerates, and that the...

Acknowledgements

This study was supported by the Academy of Finland. REFERENCES Ahmed, I. and Patton, T. F. 1985 . Invest. Ophthalmol. Vis. Sei. 26, 584-587. Ahmed, I. and Patton, T. F. 1986 . Int. J. Pharm. 34, 163-167. Ahmed, I., Gokhale, R. D Shah, M. V. and Patton, T. F. 1987 . J. Pharm. Sei. 76, 583-586. Anderson, J. A. 1980 . Arch. Ophthalmol. 98, 350-353. Armaly, M. F. and Rao, K. R. 1973 . Invest. Ophthalmol. 12, 491-496. Ashton, P., Podder, S. K. and Lee, V. H. L. 1991 . Pharm. Res. 8, 1166-1174....

Ethylcellulose

It was found that the time for release of sodium phenobarbitone from ethylcellulose microcapsules increased as the core wall ratio decreased. With a constant core wall ratio, the small microcapsules released their contents more rapidly than the larger ones Jalsenjak etal., 1976 . In a series of papers Donbrow and Benita 1977 investigated the effect of polyisobutylene on the coacervation of ethylcellulose. Ethylcellulose and polyisobutylene were dissolved in cyclohexane and the solution was...

Gelatinpectin

Microglobule size, morphology and recovery of pectin-gelatin coacervates were investigated by McMullen and coworkers 1982 . Coacervates were prepared by combining solutions of pectin and Type A gelatin in varying ratios at 45 C with stirring and adjusting the pH with NaOH solution. After 2min the pH was lowered with 0.5 N HC1 and after stirring for 30min, 5 ml of 37 formaldehyde solution were added. After cooling and decanting, the microcapsules were suspended in glycerin and then treated with...

Yield stress from compaction studies

Compaction studies, because they mimic the tabletting process, offer an ideal method for assessing the mechanical properties of powders. In powder compaction a specific method used to evaluate the average stress of a material during compression relies on the observations of Heckel 1961a,b who found that for materials that plastically deform, the relative density of a material, D, could be related to the compaction pressure, P, by the equation Unfortunately, considerable deviations of the...

Control of wet granulation

It is outside the scope of this chapter to discuss production aspects of agglomeration processes. The readers are referred to literature on instrumentation for the control of wet granulation, for example the review by Kristensen and Schaefer 1987 which includes a chapter on end-point control of wet massing methods and Werani 1988 showing the benefits of power consumption measurements for production purposes. However, a few comments on end-point control are given in order to illustrate their...

Various polymers

Three polymers have been used to encapsulate a hydrophobic drug Seiyaku, 1980 . For example, polystyrene was dissolved in an organic solvent which was immiscible with water. A hydrophobic drug was then incorporated into the solution and then this core material was dissolved in an enteric high-polymer electrolyte for example, methylacrylate. Coacerva-tion was then carried out with a solution of gelatin at an appropriate pH and cooling. Thus the drug is surrounded by the high-polymer and a coac...