Release of flurbiprofen from poloxamer 407 gel

Release rates of flurbiprofen from transdemal gels made of poloxamer 407 were evaluated using a membraneless diffusion cell in order to study the effects of formulation variables on flurbiprofen release such as poloxamer 407 (17.5–25%), drug (0.1–1.0%), ethanol (10–20%), PG or PEG 300 (5–15%) concentrations and gel pH (3–7). Isopropyl myristate was employed as a receptor medium for the drug released from the gel. The diffusion coefficient of flurbiprofen decreased linearly as the amount of poloxamer 407 and the drug in the gel increased. The release rate of flurbiprofen was gel pH-dependent and the diffusion coefficient of the drug in the gel increased as the pH of the gel increased. The addition of more ethanol in the gel increased the drug release, resulting from the increase of the thermodynamic activity of the drug in the aqueous phase of the gel. However, the concentration effects of PG and PEG 300 on the release rate of flurbiprofen were negligible over the concentration range used.     

Drug Release From Hydrocolloid Embeddings with High or Low Susceptibility to Hydrodynamic Stress

Purpose. The subject of the study was the influence of hydrodynamic stress on the drug release from direct compressed hydrocolloid embeddings. Additionally a correlation between the release kinetics and different polymer characterising parameters was attempted. Methods. The drug release was fitted to an expanded Korsmeyer equation to describe the release kinetics. The influence of the stirring rate of the paddle in the USP paddle apparatus on the Mean Dissolution Time (MDT) was expressed as quotient of the MDT's at the stirring rate of 200 and 100 min^–1. Results. If the drug release followed the square root of time kinetics, nearly no effect of the agitation speed on the release rate was observed. To achieve this diffusion controlled drug release the developing gel layer had to be hydrated very well and resistant against erosion (viscosity of at least 4000 mPa · s of the 2% polymer solution and a small expansion of the swelling gel especially at the beginning of the release). The erosion controlled zero order release was generally much affected by the hydrodynamic stress except for some hydrocolloids with incomplete swelling. Thus, it was possible to define a new release mechanism, the polymer particle erosion. The drug release was controlled by the attrition of partially swollen polymer particles and not by the polymer dissolution or drug diffusion. Conclusions. Polymer particle erosion or diffusion control should be the release controlling mechanisms for negligible influence of hydrodynamic stress.     

New Insight into the Role of Polyethylene Glycol Acting as Protein Release Modifier in Lipidic Implants

Purpose It has recently been shown that the addition of polyethylene glycol 6000 (PEG) to lipidic implants fundamentally affects the resulting protein release kinetics and moreover, the underlying mass transport mechanisms (Herrmann, Winter, Mohl, F. Siepmann, & J. Siepmann, J. Control. Release, 2007). However, it is yet unclear in which way PEG acts. It was the aim of this study to elucidate the effect of PEG in a mechanistic manner. Materials and Methods rh-interferon α-2a (IFN-α)-loaded, tristearin-based implants containing various amounts of PEG were prepared by compression. Protein and PEG release was monitored in phosphate buffer pH 4.0 and pH 7.4. IFN-α solubility and stability were assessed by reverse phase and size exclusion HPLC, SDS PAGE, fluorescence and FTIR. Results Importantly, in presence of PEG IFN-α was drastically precipitated at pH 7.4. In contrast, at pH 4.0 up to a PEG concentration of 20% no precipitation occurred. These fundamental effects of PEG on protein solubility were reflected in the release kinetics of IFN-α from the tristearin implants: At pH 7.4 the protein release rates remained nearly constant over prolonged periods of time, whereas at pH 4.0 high initial bursts and continuously decreasing release rates were observed. Interestingly, it could be shown that IFN-α release was governed by pure diffusion at pH 4.0, irrespective of the PEG content of the matrices. In contrast, at pH 7.4 both—the limited solubility of the protein as well as diffusion through tortuous liquid-filled pores—are dominating. Conclusions For the first time it is shown that the release of pharmaceutical proteins can be controlled by an in-situ precipitation within inert matrices.     

Controlled Drug Release of Smart Magnetic Self-Assembled Micelle,Kinetics and Transport Mechanisms

Magnetic nanocarriers have been extensively used as a potential drug release system for breast cancer therapy. This work investigates drug release kinetics and transport mechanisms of dasatinib (DAS) anticancer drugs encapsulated in nanomagnetic self-assembled micelles. The drug release kinetics of DAS from the nanomagnetic micelles (NMM) was predicted by fitting the drug release experimental data to four different empirical models at pH values 7.4 and 5. Moreover, a simple mathematical model that can predict the drug release from bulk eroding polymer matrices has been developed using the COMSOL Multiphysics® program. The diffusional egress of the DAS release through the NMM was carried out by evaluating the diffusion coefficients inside NMM using Fick's second law and diffusion coefficients in the solution utilizing the Stokes-Einstein equation. The results revealed that NMM exhibited a superior sustained drug release rate in acidic conditions compared to the neutral state. The Peppas-Sahlin and COMSOL models gave the best fitting for the experimental drug release data and eroding matrices obtained from free DAS, DAS-micelles, and DAS-magnetic micelles at both pH values with correlation coefficients reached to 0.99. The transport mechanisms results showed a Fickian diffusion mechanism controlled with the highest diffusion coefficients of NMM in acidic conditions, while a significant relaxation contribution was observed at the neutral state.     

Evaluation of injection moulding as a pharmaceutical technology to produce matrix tablets

The aim of this study was to develop sustained-release matrix tablets by means of injection moulding and to evaluate the influence of process temperature, matrix composition (EC and HPMC concentration) and viscosity grade of ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) on processability and drug release. The drug release data were analyzed to get insight in the release kinetics and mechanism. Formulations containing metoprolol tartrate (30%, model drug), EC with dibutyl sebacate (matrix former and plasticizer) and hydrophilic polymer HPMC were extruded and subsequently injection moulded into tablets (375 mg, 10 mm diameter, convex-shaped) at temperatures ranging from 110 to 140 °C. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4 mPa s) showed an incomplete drug release within 24 h (<50%). Increasing production temperatures resulted in a lower drug release rate. Substituting part of the EC fraction by HPMC (HPMC/EC-ratio: 20/50 and 35/35) resulted in faster and constant drug release rates. Formulations containing 50% HPMC had a complete and first-order drug release profile with drug release controlled via the combination of diffusion and swelling/erosion. Faster drug release rates were observed for higher viscosity grades of EC (Mw > 20 mPa s) and HPMC (4000 and 10,000 mPa s). Tablet porosity was low (<4%). Differential scanning calorimetry (DSC) and X-ray powder diffraction studies (X-RD) showed that solid dispersions were formed during processing. Using thermogravimetrical analysis (TGA) and gel-permeation chromatography no degradation of drug and matrix polymer was observed. The surface morphology was investigated with the aid of scanning electron microscopy (SEM) showing an influence of the process temperature. Raman spectroscopy demonstrated that the drug is distributed in the entire matrix, however, some drug clusters were identified.     

Drug release from extruded solid lipid matrices: Theoretical predictions and independent experiments

The aim of this study was to use a mechanistically realistic mathematical model based on Fick‘s second law to quantitatively predict the release profiles from solid lipid extrudates consisting of a ternary matrix. Diprophylline was studied as a freely water-soluble model drug, glycerol tristearate as a matrix former and polyethylene glycol or crospovidone as a pore former (blend ratio: 50:45:5% w/w/w). The choice of these ratios is based on former studies. Strains with a diameter of 0.6, 1, 1.5, 2.7 and 3.5 mm were prepared using a twin-screw extruder at 65 °C and cut into cylinders of varying lengths. Drug release in demineralised water was measured using the USP 32 basket apparatus. Based on SEM pictures of extrudates before and after exposure to the release medium as well as on DSC measurements and visual observations, an analytical solution of Fick’s second law of diffusion was identified in order to quantify the resulting diprophylline release kinetics from the systems. Fitting the model to one set of experimentally determined diprophylline release kinetics from PEG containing extrudates allowed determining the apparent diffusion coefficient of this drug (or water) in this lipid matrix. Knowing this value, the impact of the dimensions of the cylinders on drug release could be quantitatively predicted. Importantly, these theoretical predictions could be confirmed by independent experimental results. Thus, diffusion is the dominant mass transport mechanism controlling drug release in this type of advanced drug delivery systems. In contrast, theoretical predictions of the impact of the device dimensions in the case of crospovidone containing extrudates significantly underestimated the real diprophylline release rates. This could be attributed to the disintegration of this type of dosage forms when exceeding a specific minimal device diameter. Thus, mathematical modelling can potentially significantly speed up the development of solid lipid extrudates, but care has to be taken that none of the assumptions the mathematical theory is based on is violated.     

Effect of Polymer Blending on the Release of Ganciclovir from PLGA Microspheres

Purpose The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(d,l-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. Methods Two grades of PLGA, PLGA 7525 [d,l-lactide:glycolide(75:25), MW 90,000–126,000 Da] and Resomer RG 502H [d,l-lactide:glycolide(50:50), MW 8000 Da], were employed in the preparation of PLGA microspheres. Five sets of microsphere batches were prepared with two pure polymers and their 1:3, 1:1, and 3:1 blends. Drug entrapment, surface morphology, particle size analysis, drug release, and differential scanning calorimetric studies were performed. In vitro drug-release data were fitted to a set of empirical sigmoidal equations by nonlinear regression analysis that could effectively predict various parameters that characterize both diffusion and degradation cum diffusion-controlled release phases of GCV. Results Entrapment efficiencies of GCV ranged from 47 to 73%. Higher amounts of GCV were entrapped in polymer blend microspheres relative to individual polymers. Triphasic GCV release profiles were observed, which consisted of both diffusion and degradation cum diffusion-controlled phases. In vitro GCV release was shortest for Resomer RG 502H microsphere (10 days) and longest for PLGA 7525 microspheres (90 days). Upon blending, the duration of release gradually decreased as the content of Resomer RG 502H in the matrix was raised. Equations effectively estimated the drug-release rate constants during both the phases with high R² values (>0.990). GCV release was slower from the blend microsphere during the initial diffusion phase. Majority of entrapped drug (70–95%) was released during the matrix degradation cum diffusion phase. Conclusions Drug entrapment and release parameters estimated by the equations indicate more efficient matrix packing between PLGA 7525 and Resomer RG 502H in polymer-blended microspheres. The overall duration of drug release diminishes with rising content of Resomer RG 502H in the matrix. Differential scanning calorimetry studies indicate stronger binding between the polymers in the PLGA 7525/Resomer RG 502H∷ 3:1 blend. Polymer blending can effectively alter drug-release rates of controlled delivery systems in the absence of any additives.     

Chitosan microspheres of aceclofenac: In vitro and in vivo evaluation

The objective of this investigation was to achieve controlled drug release of Aceclofenac (ACE) microspheres and to minimize local side-effects in the gastrointestinal tract (GIT). Sustained release chitosan microspheres containing ACE were prepared using double-emulsion solvent evaporation method (O/W/O). Chitosan microspheres were prepared by varying drug to polymer ratio (1:3, 1:4, 1:5 and 1:6). Microspheres were characterized for morphology, swelling behavior, mucoadhesive properties, FTIR and DSC study, drug loading efficiency, in vitro release, release kinetics, and in vivo study was performed on rat model. ACE-loaded microspheres were successfully prepared having production yield, 57–70% w/w. Drug encapsulation efficiency was ranging from 53–72% w/w, Scanning electron microscopy (SEM) revealed particle size of microspheres was between 39 and 55 μm. FTIR spectra and DSC thermograms demonstrated no interaction between drug and polymer. The in vitro release profiles of drug from chitosan microspheres showed sustained-release pattern of the drug in phosphate buffer, pH 6.8. In vitro release data showed correlation (r² > 0.98), good fit with Higuchi/Korsmeyer-Peppas models, and exhibited Fickian diffusion. ACE microspheres demonstrated controlled delivery of aceclofenac and apparently, no G.I.T. erosion was noticed.     

Influence of Various Pharmaceutical Factors on Drug Release from Matrix Tablets

The influence of various pharmaceutical factors on the release of active substances from matrix tablets based on interpolyelectrolyte complexes of poly(methacrylic acid) and poly(ethylene glycol) has been studied. By varying these factors, it is possible to control the drug release kinetics and create new medicinal forms with preset properties. The most important factors in this respect are the polymer fraction in the composition and the character of interaction between the active substance and matrix components. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 5, pp. 40 – 45, May, 2005.     

Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers

Abstract

Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12?h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12?h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.     

Diffusion model for the study of a drug from the hydrophilic matrix of a transdermal therapeutic system through a model polymeric membrane

Conclusions The kinetics of drug supply described above from gel-like hydrophilic matrices of a TTS through human skin, or a polymeric membrane imitating itin vitro, are analogous to the kinetics of the release of a drug from a reservoir TTS through an attached polymeric membrane controlling the rate. Studying the kinetics of drug supply from diffusion matrices of TTS through a polymeric membrane imitating skin enables modeling of the kinetics of transdermal drug supplyin vitro andin vivo. The adequacy of such modeling is determined by the correlation between the diffusion coefficients of the drug in the membrane and skin epidermis and the distribution coefficients of the drug between skin and matrix or between membrane and matrix, which are subject to experimental determination.The transdermal supply of drug with kinetics of zero order (i.e. at a rate constant with time) may be effected from a TTS of the membrane-reservoir type containing a membrane specially controlling the rate or from a matrix TTS. In the latter case the function of the membrane controlling the rate of drug supply is fulfilled by the human skin at the point of application of the TTS, while the TTS diffusion matrix acts as a reservoir containing drug on the skin surface and limits the maximally achievable rate of drug release from the TTS to the skin according to equation 12. The competence of such an approach is occasionally questioned because of fears that the permeability of skin for a drug depends markedly on the point of application of the TTS and on the special features of the patient's skin. The effect of skin permeability at the point of application on the rate of transdermal drug supply has been studied well in [21] and a standard place for the application of a TTS may be the correct choice. The vast scope for the clinical application of the various TTS available at the present time indicates that individual variability of skin permeability is not so great and may be displayed mainly by a reduced permeability of the skin for a drug. Unlike membrane-reservoir TTS the majority of matrix TTS may be divided into portions of various size without disturbing their efficiency. This raises the possibility of continuously regulating the dose (by the area of application for TTS of this type).Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 10, pp. 38–45, October, 1994.     

Release mechanisms of a sparingly water-soluble drug from controlled porosity-osmotic pump pellets using sulfobutylether-beta-cyclodextrin as both a solubilizing and osmotic agent

The purpose of this work is to delineate the release mechanisms of a sparingly water-soluble drug, prednisolone (PDL), from a microporous or controlled porosity-osmotic pump pellet (CP-OPP) using sulfobutylether-beta-cyclodextrin (CD) as both a solubilizing and osmotic agent. All factors, osmotic and diffusional, influencing drug release as described by the Theeuwes and Zentner equation were partially demonstrated in an earlier paper1 and are further quantitatively evaluated here to determine whether the equation may be applied to CP-OPPs. The PDL release rate from the CP-OPPs containing precomplexed PDL follows the zero-order kinetics for up to 30-40% of drug release during the first 1-2 h and subsequently nonzero order kinetics. The zero-order drug release phase reveals the main contribution is from osmotic pumping with a negligible diffusion component, resulting from the nearly constant driving forces in the system. The nonzero order drug release phase is associated with the dynamic changes in the system (e.g., declining osmotic driving force and greater diffusion component with time). In addition, the parameters related to membrane characteristics were determined, and the effect of viscosity was evaluated for the pellet system. The membranes coated on the CP-OPPs are less permeable to water or solutes than the membranes coated on the previously reported tablets. The viscosity due to the CD decreases as a function of CD concentration, which partly affects the observed drug release profiles. The viscosity effect of CD is significant and captured in a hydraulic permeability term.     

Modelling of release kinetics of drugs from irradiated NaCMC matrix

The purpose of this work was to study the release kinetics of an active substance from a solid structure after irradiation, in order to examine the possible modifications induced in drug delivery. This method of sterilization seems to be convenient for obtaining sterile parenteral or ophthalmic dosage forms. The problem of controlled release of drug from a polymeric matrix is very complex. In this case, the phenomena take place under transient diffusion and the transfer of matter is controlled by diffusion. The modelling of the process has been successfully tested, by comparing experimental and calculated values. The diffusivity of the liquid through the various dosage forms increases significantly with irradiation.     

Diffusion transport in interpolyelectrolyte matrix systems based on chitosan and Eudragit L100

With a view to the development of new controlled drug delivery systems, the formation of an interpolyelectrolyte complex (IPEC) between chitosan (CTS) and Eudragit L100 (L-100) has been studied. The structure of this IPEC is such that two maxima are observed in the curves of IPEC swelling in the media with different pH values. The release of a model drug (ibuprofen) from IPEC-based tablets is significantly retarded, and this delay can be controlled by changing the molecular weight of CTS in the IPEC composition. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 12, pp. 44–46, December, 2005.     

Sustained Release of Acetaminophen from Heterogeneous Matrix Tablets: Influence of Polymer Ratio,Polymer Loading,and Co-active on Drug Release

ABSTRACT

The aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 lb. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (≥ 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.     

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure.     

Potential carriers for controlled drug delivery based on Eudragit<Superscript>®</Superscript> EPO/L100 – 55 interpolyelectrolyte complexes. part 2: comparative evaluation of diffusion transport properties

New interpolyelectrolyte complexes (IPECs) between oppositely charged types of Eudragit^? EPO and Eudragit^? L100 – 55 were investigated with a view to their application in oral controlled drug delivery systems. Monitoring of microenvironmental changes of polycomplex matrices in simulated gastro-intestinal fluids showed that all IPECs could have different pH-sensitivity characteristics. Evaluation of the diffusion transport properties of the investigated IPECs with diclofenac sodium confirmed that their swellability and release characteristics were closely correlated. The main possible mechanisms of control over the delivery of drugs to the desired regions of the gastro-intestinal tract are found. The results confirm that the proposed IPEC matrices have great potential to be used for controlled drug delivery.     

Zero-Order Drug Release from Hydrocolloid Matrices

Matrices are manufactured by direct compression of a powder mixture of a polymer, e.g., methylhydroxypropyl cellulose (MHPC) or polyvinylalcohol (PVAI), and a drug. The following factors that can influence the drug release mode were investigated at constant surface: (i) polymer solution viscosity, glass transition temperature, and swelling; (ii) drug concentration in the matrix and solubility; and (iii) conditions of release experiment (hydrodynamics). In the case of zero-order release profiles (hydrocolloids with low viscosities), only the dissolution of the polymer appears to control the drug release rate. Factors accelerating polymer dissolution resulted in higher release rates. Comparison of swollen and dry hydrocolloid matrices shows that the duration and kinetics of drug release were not controlled by the swelling front moving into the dry polymer, and water penetration and relaxation were not rate controlling. Therefore, the glass transition temperature had no effect on drug release from these hydrocolloids. The higher the hydrodynamic stress exerted on the eroding hydrocolloid, the faster the resulting drug release as a result of accelerated polymer dissolution. With hydrocolloids of very high viscosity the polymer dissolution is slow, and drug relese from the swollen gel appears to be controlled by diffusion according to kinetics of the Higuchi type.     

Matrix embedded microspherules containing indomethacin as controlled drug delivery systems

This work is focused on the development of controlled drug delivery systems using different wax/fat embedded indomethacin (IM). Discrete wax/fat embedded microspherules containing indomethacin were prepared by using cetostearyl alcohol, paraffin wax and stearic acid by employing emulsification-phase separation method. These matrices have been used as barrier coatings due to their hydrophobic nature. Chemically inert and tasteless nature of wax/fats promotes their use as taste masking agents for bitter drugs. Various waxes and fats are available having different physicochemical properties to suit the needs of formulation. Methyl cellulose (MC) 1% w/v, sodium alginate (SA) 0.5% w/v and Tween-80 (TW) 1% w/v were used as emulgents. The resulting microspherules were discrete, large, spherical and also free flowing. It is revealed from the literature that natures of wax/fat emulgents were found to influence the rate of drug release. In the present work the drug content in all the batches of microspherules were found to be uniform. The rate of drug release corresponded best to first order kinetics, followed by Higuchi and zero-order equations. The release of the model drug from these wax/fat microspherules was prolonged over an extended period of time and the drug release mechanism followed anomalous (non-Fickian) diffusion controlled as well as Super Case II transport. Among the three matrix materials used, paraffin wax retarded the drug release more than the other two. Surface characteristics of microspherules have been studied by Scanning Electron Microscope (SEM). A fair degree rank of correlation was found to exist between the size and release retardation in all the three-wax/fat emulgent combinations.