A Comparative Study of Acyclovir Microencapsulation by ... · Naik and Raval: Acyclovir Microencapsulation by Novel Solvent Evaporation-Matrix Erosion and Spray Drying Techniques

Naik and Raval: Acyclovir Microencapsulation by Novel Solvent Evaporation-Matrix Erosion and Spray Drying Techniques 1627

Research Paper

A Comparative Study of Acyclovir Microencapsulation by Novel Solvent Evaporation-Matrix Erosion and Spray Drying Techniques

D.R. Naik and J.P. Raval Department of Pharmaceutical Chemistry, Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences(ARIBAS), New Vallabh Vidyanagar – 388 121, District Anand, Gujarat, India.

Received October 05, 2011; accepted March 17, 2012

ABSTRACT

Designing and evaluating a multiparticulate controlled release dosage form, to increase the efficacy of acyclovir (a selective antiherpes agent). Spray drying technique for microsphere production is compared with novel solvent evaporation-matrix erosion technique for variable drug loading in different concentration of ethyl cellulose. The microspheres were characterized for physicochemical properties. The microspheres sizes were ranged from 7-25 μm. The spray dried microspheres had better encapsulation efficiency (up to 91%) compared to that of novel solvent evaporation-matrix erosion technique microspheres. Scanning electron microscopy confirmed spherical geometry due to high cross-

linking density. Differential scanning calorimetry, Fourier-transform infrared spectroscopy and x-ray diffraction studies showed chemical stability and intactness of entrapped drug in the microspheres. In vitro release of acyclovir from spray dried microspheres continued for longer period compared to novel solvent evaporation-matrix erosion method. Overall, the release studies depended on the concentration of ethyl cellulose, extent of drug loading, and the technique used to prepare microspheres. Thus, marked retardation of drug release may provide a useful effective anti-retroviral drug therapy.

KEYWORDS: Acyclovir; ethyl cellulose; microspheres; novel solvent evaporation-matrix erosion technique; spray drying technique.

Introduction The potential application of microencapsulation in

pharmaceutics has a great deal of attention over the past several years (Delgado et al., 2002). Microencapsulation is one process used to control and retard drug release and hence it prolongs therapeutic activity (Bakan and Anderson, 1976). It offers greater effectiveness, lower toxicity, lower dosing and more lasting stability than conventional formulations. Many microencapsulation techniques have been developed till date such as solvent evaporation technique (Choudhury and Kar, 2009), phase separation method (Zhang et al., 2005), spray drying (Cortesi et al., 2007) and polymerization (Jeong et al., 2005).

Spray drying was developed as a convenient method for increasing solubility of poorly water-soluble drugs and for drying heat-sensitive materials like amino acids, antibiotics, pepsin and similar enzymes with minimal loss of activity (Alanazi et al., 2007). So, selection of technique depends on the nature of drug, polymer and the intended use. An appropriate selection of the polymeric matrix and method of preparation is necessary in order to develop a successful microparticulate delivery system.

Acyclovir (ACY) [9-(2-hydroxyethoxymethyl) guanine] a synthetic purine nucleoside analog, is the first licensed drug for the treatment of herpes viruses (Herpes Simplex Virus (HSV-1), Herpes Zoster and certain strains of Varicella Zoster virus) (Devi and Bhosale, 2009; Jalon et al., 2003). It is having short biological half life of 2-3 hours (Gupta et al., 2010) and low bioavailability of 10-20% (Sweetman, 2002). Hence, it is considered as an ideal candidate for controlled drug delivery. Various approaches are made to improve the concentration of ACY in the plasma over an extended period of time there by reducing the drug dosage and unwanted toxic effects. Microspheres are the ideal candidate for controlled drug delivery of the drugs with short biological half life and lower bioavailability.

The present study is aimed at formulating ACY to develop an economically viable microparticulate ACY delivery system for better control of chronic recurrent herpes infection utilizing the ethyl cellulose as matrix forming polymer. Ethyl cellulose, being a biocompatible and non-biodegradable polymer, is studied extensively as encapsulating material for the controlled release of pharmaceuticals (Muniyandy and Boddapati, 2011). In this study, we have undertaken a detailed study to prepare microspheres using novel solvent evaporation-

International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 5 • Issue 1 • April – June 2012MS ID: IJPSN-10-05-11-NAIK

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1628 Int J Pharm Sci Nanotech Vol 5; Issue 1 • April−June 2012

matrix erosion (Muniyandy and Boddapati, 2011) and spray drying technique (Fu et al., 2002; Gavini et al., 2003; Gavini et al., 2004). The microspheres prepared by these two techniques are compared for their encapsulation efficiency and release kinetics. Microspheres with variable ethyl cellulose concentration and different drug loading i.e. various drug/polymer ratios have been prepared to get optimum release of drug for a prolonged period. The effects of polymer concentration and the method of production of microspheres, on the release characteristics and physiochemical properties of the microspheres were investigated.

Materials and Methods

Chemicals and Drugs Acyclovir was procured as a gift sample from Cadila

Pharmaceuticals Ltd. (Ahmedabad, India). Ethyl cellulose (100.000 cps, ethoxyl content: 49) was purchased from Sigma - Aldrich Chemical Company, Inc. (Milwaukee, WI, USA). Polyvinyl alcohol (Molecular weight=30,000-20,000) and dichloromethane was purchased from S.D. Fine Chemicals, Mumbai, India. Dialysis membrane-110 was purchased from Himedia Laboratories Pvt. Ltd., Mumbai, India. Double-distilled water was used throughout the work. All other reagents and solvent used were of analytical grade.

Preparation of Microspheres by Spray Drying Technique Ethyl cellulose (2% by weight, 3% by weight) was

dissolved in dichloromethane. The aqueous phase containing ACY equivalent to 10%, 15% and 20% of dry weight of the polymer, was added drop wise to the polymer solution and were kept under magnetic stirring (Remi, India, approximately 500 rpm) during the entire spraying process at ambient temperature. Drug-loaded microspheres based on cellulosic polymers were prepared using a (LU-222 Advance Spray Drier, Labultima, Mumbai, India), cocurrent flow type, equipped with standard nozzle of 0.7 mm inner diameter (Patel et al., 2008). The liquid was fed to the nozzle with peristaltic pump. The volume of dispersion was 150 ml. The liquid was atomized by the force of the compressed air, and blown together with a hot air to the chamber where the solvent in the droplets was evaporated. The dry product was then collected in collection vessel, weighed and kept

under vacuum for 48 hours before use. Process conditions used were as follows: inlet air temperature, 55°C + 5°C; outlet air temperature, 45°C + 5°C; and feed spray rate, 10 ml/min, and pressure bar at ~2 atm. The compositions of various formulations along with formulation codes are summarized in Table 1. Each formulation was produced in triplicate.

Preparation of Microspheres by Novel Solvent Evaporation-Matrix Erosion Technique Microspheres containing ACY prepared by novel

solvent evaporation-matrix erosion technique (Muniyandy and Boddapati, 2011). Ethyl cellulose 2% and 3% (W/W) was dissolved in 150 ml dichloromethane. ACY equivalent to 20% (W/W) of dry weight of ethyl cellulose was dissolved separately in distilled water. The above two solutions were mixed and stirred thoroughly to form a homogeneous solution. This mixture was dispersed in liquid paraffin, and stirred with the help of magnetic stirrer (Remi, India, approximately 500 rpm) for about 6 hours at room temperature to form rigid spherical spheres. Microspheres were filtered using Whattman filter paper, washed with 15 ml of hexane thrice and dried at 40oC overnight.

Determination of Drug Loading and Encapsulation Efficiency To determine the average drug content, a sample of

100 mg accurately weighed drug loaded microspheres were crushed in porcelain mortar and suspended in phosphate buffer solution (PBS) (pH 7.4) and volume was made up to 100 ml. After filtration, suitable dilutions of the filtrate were prepared and the quantity of ACY was estimated at 254 nm using UV-visible spectrophotometer (SP-3000+, Tokyo, Japan). The amount of ACY was calculated by using regression equation of the calibration curve. All the readings were carried out in triplicate. The percent drug loading and percent encapsulation efficiency of the microspheres were calculated using equation (1).

% Drug loading =

⎛ ⎞⎜ ⎟⎝ ⎠

Weight of drug in microspheres×100

Weight of microspheres …..(1)

% Encapsulation Efficiency =

Drug loading

The oritical loading⎛ ⎞⎜ ⎟⎝ ⎠

%×100

% …..(2)

TABLE 1 Composition, production yield, mean particle size and encapsulation efficiency of different formulations.

Formulation Code

Ethyl cellulose (%, w/w)

Acyclovir (wt %)

Dichloro-methane (ml)

Producrion yield (M+SD) (%)

Volume mean particle size (M+SD) (μm)

Drug Loading (%)

Encapsulation Efficiency (%)

F1 2 10 150 35.90+0.71 9 . 5 +0 . 8 3 8.838 8 8 . 3 8 F2 2 15 150 41.55+1.63 8 . 5 +0 . 9 5 12.663 8 4 . 4 2 F3 2 20 150 42.42+1.02 7 . 8 +0 . 7 5 16.168 8 0 . 8 4 F4 3 10 150 46.34+0.82 1 2 . 5 +0 . 6 2 9.333 9 3 . 3 3 F5 3 15 150 46.83+1.14 1 0 . 2 +0 . 7 0 13.767 9 1 . 7 8 F6 3 20 150 50.03+0.62 8 . 9 +0 . 2 6 18.238 9 1 . 1 9 F7a 2 20 150 84.76+0.89 2 4 . 4 +0 . 8 3 8.148 4 9 . 3 2 F8a 3 20 150 87.29+1.14 1 9 . 4 +0 . 4 3 10.312 4 4 . 5 6

aMicrospheres prepared by solvent evaporation technique.


Yield of Microspheres Microspheres recovered at the end of preparation

were weighed and the yield was calculated as a percentage of the total amounts of polymer and drug added during the preparation of microspheres.

Scanning Electron Microscopy The surface morphology and surface characteristics of

samples were studied by scanning electron microscopy (SEM). The powder samples were dispersed in water, and were dropped onto metal stubs and allowed to dry in air under ambient conditions. Each sample was coated with gold under vacuum prior to examination by SEM (JSM-5410, Jeol, Japan). The surface was scanned samples using a gaseous secondary electron detector (working pressure: 0.8 torr, acceleration voltage: 30 kV, XL 30, Philips (Eindhoven, The Netherlands)).

Particle Size Studies Particle size was measured by dynamic laser light

scattering model Halos–BF (Symantec, Germany). Sizes of the completely dried microspheres of different formulations were measured by dry sample technique using a dry sample adapter. The completely dried particles were placed on the sample tray with an inbuilt vacuum under a compressed air system, which was used to suspend the particles. The laser obscuration range was maintained between 0.1-875 μm. The volume mean diameter (VMD) was recorded. After the measurement of particle size of each sample, the dry sample adopter was cleaned thoroughly to avoid cross contamination. Each batch was analyzed in triplicate, but average values were considered in data analysis.

Fourier Transform Infrared Spectroscopy The spectra were recorded for pure drug, drug-loaded

microspheres and blank microspheres using Fourier transform infrared spectroscopy (FTIR; Spectrum GX, Perkin Elmer, Chicago, USA) to investigate the possible chemical interactions between ACY and ethyl cellulose. Samples were prepared in potassium bromide disks (0.02%W/W in potassium bromide) which were made at 300 kg/cm2 pressure. The spectrum was recorded in the wavelength region of 400–4000 cm-1 and the resolution of 0.15 cm-1 at scan speed 10 scan/s.

Differential Scanning Calorimetry Differential scanning calorimetry (DSC) curves were

obtained with DSC-PYRIS-1 (Perkin Elmer). Scans of drug, blank microspheres, and drug-loaded microspheres were obtained. The analysis was performed with a heating range of 50°C-300°C and a rate of 10°C/ min.

X-ray diffraction Studies X-ray diffraction (XRD) patterns were obtained using

Philips X-ray diffractometer (X pert), with voltage of 40

kV, current of 40 mA and Cu α-radiation source in the range of 3° to 136° of 2θ with 1 second of scan time. Pristine ACY and ACY-loaded microspheres were evaluated by powder XRD technique using the powder XRD method for their crystalline nature.

Drug Release Study The in vitro drug release study was performed using

USP XXIV basket apparatus (Electrolab, TDT-06T, Mumbai, India) at 37°C and at 100 rpm in 900 ml of 0.1 mol L−1 HCl at pH 1.2 and phosphate buffer (pH 7.2) as a dissolution medium (Soni et al., 2008) i.e. in gastric and intestinal pH conditions. Microspheres equivalent to 100 mg of ACY were used for the test. 5 ml of sample solution was withdrawn through a sampling syringe at predetermined time intervals, filtered through a 0.45 mm membrane filter, diluted suitably. The samples were analyzed by UV-visible spectrophotometer (SP-3000PLUS, Japan) at 254 nm (Martinez-Sancho and Herrero-Vanrell, 2003). The volume withdrawn was replenished with an equal volume of fresh dissolution medium pre-warmed to 37°C immediately after withdrawal of the test sample. Percentage drug dissolved at different time intervals was calculated using the calibration curves constructed from the reference standards.

Release Kinetics Data obtained from in vitro drug release study, were

fitted to various kinetic equations (Costa and Lobo, 2001) to find out the mechanism and kinetics of drug release from microspheres. The kinetic equations used were zero order equation, first order equation and Higuchi model. Qt = k0 t …..(1)

Where, k0 is zero-order rate constant expressed in units of concentration/time and t is the time. ln Qt = ln Q0 – k1 t …..(2)

Where, k1 is first order constant. Qt = kH t1/ 2 …..(3)

Where, kH is the Higuchi constant reflecting the design variables of the system.

The following plots were made; Qt vs. t (zero order kinetic model), log (Q0 - Qt) vs. t (first order kinetic model) and Qt vs. square root of t (Higuchi model) (Higuchi, 1963), where Qt is the total amount of drug released at time t and Q0 is the initial amount of the drug present in the microspheres. The rate constants were calculated for the respective models. Further, in order to define a model which will represent a better fit for the formulation, the first 60% drug release data fitted in Korsmeyer-Peppas (Korsmeyer, 1983) equation. Qt = k tn …..(4)

Where, k is the kinetic constant and n is the diffusion exponent, a measure of the primary mechanism of drug release.


Results and Discussion The novel solvent evaporation-matrix erosion method

and spray-drying technique described here are able to effectively encapsulate ACY into EC microspheres.

Determination of Loading Efficiency Table 1 lists theoretical compositions, production

yield, actual drug contents and encapsulation efficiencies of microspheres obtained both the techniques. The results indicated that the encapsulation efficiencies of microspheres prepared with spray drying technique ranged between 80-92%. While encapsulation efficiencies ranged between 40-50% for the microspheres prepared with novel solvent evaporation-matrix erosion technique. It could be seen that the encapsulation efficiencies of the microspheres prepared with spray drying technique were found to be quite high. As the concentration of the polymer increases, the encapsulation efficiencies increases which might be due to formation of thick wall of polymer. As the drug loading increases the encapsulation efficiencies slightly decreases, which might be caused by damaged microspheres. Damaged microspheres with surface irregularities, fragmentation or holes are likely to cause the loss of a substantial amount of drug during the spray microencapsulation process.

Determination of Percentage Yield Production yield is expressed as the weight

percentage of the microspheres obtained with respect to the initial amount of drug and polymer used for the preparation. Production yields were found to be between 30% + 40% for the microspheres prepared with spray drying technique while production yields ranged between 80% + 90% for the microspheres with modified novel solvent evaporation-matrix erosion technique. The low values for spray dried microspheres is because for the preparation of each batch of microspheres, relatively low volumes of feed solution is sprayed (150 ml) and also the structure of the spray-dryer apparatus does not have a trap attached for the recovery of the smaller and lighter particles which are exhausted by the aspirator. Furthermore the microspheres adhere to the cyclone walls leading to the loss of material during spray-drying process (Martinac et al., 2005). The comparison of batches, achieved from the spraying of solution of increasing concentration and same composition, shows that the concentration of feed solutions does not influence production yields.

Particle Size Studies The spray drying technique has produced

microspheres in the size range of 7-13 µm for different formulations which indicated the narrow size distribution it may be because of lower viscosity of the spray solution, aspirator speed, and feed pump flow rate.

However, in case of microspheres prepared from modified novel solvent evaporation-matrix erosion technique, the particle size was in the size range of 19-25 µm, which is bigger than those of the particles prepared by spray drying technique. It was also noted that increasing the polymer concentration slightly increased the size of microspheres (Gavini et al., 2008) and the increased atomization nozzle flow reduced the particle size (Stahl et al., 2002).

Scanning Electron Microscopy Surface morphological studies on the shape of the

prepared systems using scanning electron microscopy indicated that the systems were almost spherical (Figure 1). It can be seen that no drug crystals were found on the microsphere surface which might be attributed to uniform removal of solvent by evaporation to produce even polymer distribution. The increase in the concentration of polymeric solution leads to alteration of morphological characteristics such as slightly rough surface of the microspheres (Chiou et al., 2001).

X-Ray Diffraction The crystalline natures of pristine ACY and ACY

loaded microspheres have been evaluated by XRD. XRD diffractograms of (a) Pristine ACY, (b) placebo microspheres, and (c) ACY loaded microsphere are presented in Figure 2. The XRD diffractograms of drug loaded microspheres did not show the same peaks as ACY, indicating that the ACY underwent a transition from a crystalline to an amorphous state. In this study, the characteristic intensities of ACY have been overlapped with the noise of the coated ethyl cellulose indicating molecular level dispersion of ACY in ethyl cellulose matrix and hence no crystals were found in ACY loaded matrices. These observations along with DSC studies confirm the amorphous nature of ACY in the formulated microspheres.

FTIR Spectroscopy The ACY identification and drug polymer

compatibility in microspheres have been evaluated by FTIR. The infrared spectrum of (a) Pristine ACY, (b) Placebo microspheres and (c) ACY loaded microsphere are presented in Figure 3. Pure acyclovir showed prominent peaks at 3462 cm-1, 3228 cm-1 and 1719 cm-1 because of hydroxyl, aromatic amine and carboxy respectively. The observations indicated that the principal FTIR absorption peaks observed in the spectra of drug were close to those in the spectra of the microspheres containing drug, indicating the stability of acyclovir during processing of microspheres. The peaks of drug-loaded microsphere are of lower intensity than the pristine drug, confirming their compatibility. The IR spectroscopy revealed that there was absence of drug–polymer interaction and they are mutually compatible.


Fig. 1. Scanning electron micrographs of (a) acyclovir loaded ethyl cellulose microspheres and (b) acyclovir loaded ethyl cellulose single microsphere.


Fig. 2. XRD Diffractogram of (a) pristine acyclovir, (b) placebo microspheres, and (c) acyclovir-loaded microspheres.


Fig. 3. FTIR spectra of (a) pristine acyclovir, (b) placebo microspheres, and (c) acyclovir-loaded microspheres.

Differential Scanning Microscopy Differential scanning calorimetry was carried out to

determine the possible interaction between drug and polymer. The DSC thermograms of pristine ACY, placebo microspheres and ACY loaded ethyl cellulose microspheres are presented in Figure 4. ACY showed a sharp endothermic peak at 258.1ºC which corresponds to the melting point of ACY. The DSC thermograms of ACY-loaded ethyl cellulose microspheres also showed a similar characteristic peak with decreased intensity showing the stability of acyclovir during processing of microspheres. The intensity of the drug peak is decreased may be due to a decrease in the degree of ACY crystallinity in ethyl cellulose microspheres at lower drug-loading, indicating a mixture of both crystalline and amorphous forms of drug in microspheres. No individual changes in the thermograms were observed for the drug and polymer mixtures, indicating that the drug exists in amorphous state and shows no interaction.

Fig. 4. The DSC thermogram of (a) pristine acyclovir, (b) placebo microspheres, and (c) acyclovir-loaded microspheres.


Drug Release Study In vitro release experiments were carried out in two

different dissolution mediums to compare the in vitro release characteristics of all the microspheres. To avoid erroneous results due to sudden temperature changes, the dissolution media (phosphate buffers) were gradually warmed to 37oC, at which all the in vitro experiments were performed. The drug-loaded microspheres of all formulations F1-F8, the percent cumulative release vs. time plots are compared to investigate the effect of method of preparation and the concentration of polymer on in vitro release profiles. The rate of drug release from the microspheres was faster in of pH 1.2 HCl (Figure 5) compared to that in pH 7.2 phosphate buffers (Figure 6). Above 20-25% of ACY was released in first 4 hours at pH 1.2. This may be due to higher solubility of drug and polymer in acidic pH, which has increased the chance for its initial quick release. Such initial burst effect is observed in all formulations and will be beneficial to achieve the effective plasma concentration after administration of ACY. However, none of the formulations showed 100% drug release.

As the concentration of ethyl cellulose increased from 2-3% the release from the microspheres decreased and was sustained for longer period which might be associated with increased thickness of the polymer matrix (Raval et al., 2011). The thick polymer matrix slows the entry of surrounding dissolution medium in to the microspheres and hence less quantity of drug leaches out from the polymer matrices of the microspheres exhibiting extended release (Natha et al., 2010). Furthermore, the differing nature of drug and the polymer, hydrophilic and hydrophobic respectively may

cause the slow release of the ACY. This indicates that the drug was retarded due to the hydrophobic and insoluble nature of the polymer used.

The microspheres prepared with modified novel solvent evaporation-matrix erosion technique showed maximum release of ACY within 44 hours where as for spray-dried formulations, maximum release was extended achieved within 13 days. Drug release from microspheres prepared by using ethyl cellulose gave good release rate retardation when compared to other polymers. From the release profiles it can be understood that the concentration of polymer, drug and the technique used for the preparation influences the release rate of the drug a lot. The formulation F6 exhibits maximum release period compared to all the formulations.

Release Kinetics The release data were fitted to models representing

zero-order, first-order, and Higuchi’s square root of time, to examine the drug release kinetics. To examine the mechanism of release the data were fitted to Korsmeyer-Peppas model. The release constants were calculated from the slope of the appropriate plots, and regression coefficient (R2) by linear regression analysis. As indicated in Table 2, the in vitro drug release of all the formulations was best explained by Higuchi’s model as the plots showed the highest linearity. Thus the drug release of ACY was proportional to square root of time. This indicates that the drug release is controlled by diffusion of the drug through the pores for all the formulations.

Fig. 5. Dissolution profiles of the microspheres containing different ratios of acyclovir: ethyl cellulose in chloridric acid (pH 1.2).


Fig. 6. Dissolution profiles of the microspheres containing different ratios of acyclovir:ethyl cellulose using phosphate buffer (pH 6.8) (a) by spray drying method and (b) by novel solvent evaporation-matrix erosion method.

TABLE 2

Correlation coefficient (r), reaction rate constants (k) and diffusion exponent (n) of the model equations applied to the release of acyclovir from ethyl cellulose microspheres.

Formulation Code

Dissolution Media (pH)

Zero Order First Order Higuchi Korsmeyer-Peppas r2 k0 r2 k1 r2 kh r2 n

F1 1.2 0.892 2.038 0.995 -0.081 0.997 11.29 0.928 0.619 6.8 0.638 6.542 0.423 -0.042 0.878 26.23 0.998 0.242

F2 1.2 0.873 3.804 0.984 -0.078 0.993 12.42 0.934 0.573 6.8 0.617 8.721 0.467 -0.036 0.863 27.54 0.992 0.259

F3 1.2 0.863 2.731 0.974 -0.093 0.986 15.73 0.912 0.548 6.8 0.675 7.546 0.406 -0.028 0.922 27.64 0.973 0.219

F4 1.2 0.937 3.339 0.987 -0.084 0.994 10.23 0.939 0.564 6.8 0.758 8.351 0.476 -0.041 0.912 26.67 0.990 0.284

F5 1.2 0.906 2.823 0.951 -0.082 0.990 11.51 0.924 0.561 6.8 0.783 6.238 0.436 -0.037 0.931 26.93 0.977 0.225

F6 1.2 0.940 2.303 0.954 -0.095 0.987 9.928 0.939 0.501 6.8 0.756 5.762 0.401 -0.027 0.943 26.09 0.980 0.304

F7a 1.2 0.812 4.017 0.977 -0.093 0.915 18.34 0.945 0.623 6.8 0.605 8.967 0.502 -0.053 0.881 30.12 0.982 0.356

F8a 1.2 0.914 4.662 0.985 -0.086 0.937 17.73 0.910 0.669 6.8 0.613 8.875 0.527 -0.051 0.871 29.98 0.973 0.329


In all trials, drug release mechanism was studied by applying the Korsmeyer-Peppas model. According to the Korsmeyer-Peppas (Korsmeyer et al., 1983), a value of the exponent, n = 0.5, 0.5<n<1, n = 1.0 indicates the Fickian diffusion, non-Fickian diffusion and purely relaxation-controlled delivery which is referred to as Case II transport, respectively (Karada et al., 2001). The results shown in Table 2 indicate that the formulations presented different mechanism of release depending on the pH of the medium. Under acidic conditions (pH 1.2), the values of diffusional exponent, n for the microspheres are greater than 0.5 indicating non-Fickian release kinetics. At pH 6.8 all the formulations has n values lesser than 0.5 indicating a Fickian release.

Conclusions In conclusion, microspheres of ACY with ethyl

cellulose polymer were produced by spray drying and novel solvent evaporation-matrix erosion technique. When compared, spray drying technique produced microspheres with high encapsulation efficiency. ACY was transformed from crystalline state to amorphous state in these microspheres as confirmed by DSC and XRD results. The dissolution rate of ACY was improved from spray dried microspheres as compared to microspheres prepared by modified novel solvent evaporation-matrix erosion technique and the release mechanism was found to be diffusion controlled. Furthermore, the higher percentage of polymer gave longer drug release profile. Thus the properties of ACY loaded ethyl cellulose microspheres was influenced by the type of formulating method, concentration of the polymer, extent of Acyclovir loading and pH of the media. On the basis of evaluation parameter, spray drying technique is found to be better than that of novel solvent evaporation-matrix erosion technique. It would be possible to prepare microparticulate controlled release systems with slow release characteristic of acyclovir successfully by spray drying technique.

Acknowledgment Authors would like to thank SICART, Vallabh

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Address correspondence to: J. P. Raval, Department of Pharmaceutical Chemistry, Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), ADIT Campus, Behind Vithal Udhognagar, New Vallabh Vidyanagar – 388 121, Dist : Anand, Gujarat, India. Email: [email protected]

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