IAJPS 2017, 4 (10), 3503-3509 Gayke Amol U et al ISSN 2349-7750

CODEN [USA]: IAJPBB ISSN: 2349-7750

INDO AMERICAN JOURNAL OF

PHARMACEUTICAL SCIENCES
http://doi.org/10.5281/zenodo.1002943

Available online at: http://www.iajps.com Research Article

FORMULATION AND EVALUATION OF SUSTAINED

RELEASE MICROSPHERES OF ROSIN CONTAINING
ATORVASTATIN CALCIUM
Gayke Amol U*, Aglawe Sachin B, Thakare Girish, Kale Nitin, Gujarathi Tanmay, jagdale
Ashok, Khandagle Sandip
S.N.D. College of Pharmacy, Babhulgaon, Yeola, Nashik, India.
Abstract:
Atorvastatin Calcium was microencapsulated using rosin by o/w emulsion solvent evaporation technique. The effect
of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and
organic solvent (dichloromethane) volume were examined. The prepared batches were characterized for
microspheres particle size distribution, encapsulation efficiency and in vitro release behavior. The study reveals that
drug:polymer ratio had a considerable effect on the entrapment efficiency, however particle size distribution of
microspheres was more dependent on the volume of dichloromethane and polyvinyl alcohol concentration rather
than on the drug: polymer ratio. Drug, polymer concentrations were varied to obtain optimum release profile for
sustaining the action of the drug.
Keywords: Atorvastatin Calcium. Rosin. Microspheres. Sustained release
Corresponding author:
Gayke Amol U, QR code
S.N.D. Coleege of Pharmacy,
Babhulgaon, Yeola,
Nashik, India

Please cite this article in press as Gayke Amol U,et al, Formulation and Evaluation of Sustained Release
Microspheres of Rosin Containing Atorvastatin Calcium, Indo Am. J. P. Sci, 2017; 4(10).

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INTRODUCTION:
Conventional oral drug administration does not are formed by the evaporation of an organic solvent
usually provide rate-controlled release or target from dispersed oil droplets containing both polymer
specificity. In many cases, conventional drug anddrug[4,7,9,10,11]. Atorvastatin calcium is a
delivery provides sharp increase in drug HMG-CoA reductase inhibitor used in the treatment
concentration often achieving toxic level and of hyperlipidemia. It has an oral bioavailability of
following a relatively short period at the therapeutic less than 12% after a 40mg oral dose. It also
level of the drug concentration eventually drops off undergoes high first pass metabolism. It is highly
until re-administration. In order to obtain maximum soluble in acidic pH and absorbed more in the upper
therapeutic efficacy, it becomes necessary to deliver part of the GIT. The major hurdle of atorvastatin is
an agent to the target tissue in the optimal amount for rate limited bioavailability. The main objective of the
the required period of time, thereby causing little present work is to formulate microspheres of
toxicity and minimal side effects [1,2]. Desired drug atorvastatin. The microspheres of atorvastatin may
release can be provided by rate-controlling improve solubility and higher dissolution rate by
membranes or by implanted biodegradable polymers decreasing particle size and increasing surface area.
containing dispersed medication. Microparticulate They may increase the patient compliance by
drug delivery systems are considered and accepted as significantly enhancement in oral bioavailability of
a reliable one to deliver the drug to the target site the drug.
with specificity, to maintain the desired concentration
at the site of interest without untoward effects [2]. MATERIALS AND METHODS:
Microencapsulation is a useful method which
prolongs the duration of drug effect significantly and Materials
improves patient compliance. Eventually the total Atorvastatin calcium candida health pharmaceutical;
dose and few adverse reactions may be reduced since Eudragit S100 Evonik Industries. Polyvinyl alcohol
a steady plasma concentration is maintained [3]. In (PVA - MW 1, 30,000) from SD fine chemicals,
recent years much research in drug delivery has been Rosin from Yucca Enterprises, Dombivilli, and
focused on degradable polymer microspheres. Thane, India were used in the study.
Administration of medication via such systems is Dichloromethane, Potassium dihydrogen phosphate,
advantageous because microspheres can be ingested Sodium hydroxide and Camphor were procured from
or injected, can be tailored for desired release profiles S.D. Fine Chemicals, Mumbai, India.
and in some cases it can provide organ-targeted
release [4-7]. The meaning of microencapsulation is Method
converting liquids to solids, altering colloidal and Microspheres of Atorvastatin calcium were prepared
surface properties, providing environmental based on o/w emulsion solvent evaporation technique
protection and controlling the release characteristics by using rosin as a polymer. Different batches of
by using the coating materials.Emulsion solvent [5], microspheres were prepared by dissolving the
phase-separation method10 and spray drying method polymer and the drug in dichloromethane and then
[8] are commonly used for the preparation of adding this oil phase in the aqueous phase (100 ml)
microspheres. The success of any microencapsulation containing various percentages of PVA as the
method depends on many factors such as the drug emulsifying agent; the mixture was emulsified by
solubility, partition co-efficiency, polymer constant stirring at 400 rpm for 4 h by using a
composition, molecular weight etc. Among the propeller stirrer (Remi, India). The dispersed drug
various microencapsulation methods, emulsion and polymer solution was immediately transformed
solvent evaporation technique is often widely used to into fine droplets, which subsequently solidified into
prepare microcapsules of water insoluble drugs rigid microspheres due to the solvent evaporation.
(within the water insoluble polymer). Microspheres The particles were collected by filtration, washed and
dried in vacuum desiccators and characterized

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Table 1: Composition of Atorvastatin calcium loaded microspheres

Ingredients (mg) F1 F1 F1 F1 F1 F1 F1

Atorvastatin calcium 200 400 600 200 200 200 200

Rosin 200 200 200 400 600 400 600

PVA 0.25% 0.25% 0.25% 0.25% 0.25% 0.25% 0.25%

Dichloromethane 10 ml 10 ml 10 ml 10 ml 10 ml 10 ml 10 ml

Water 100 ml 100 ml 100 ml 100 ml 100 ml 100 ml 100 ml

Camphor --- --- --- --- --- 200 200

Drug-Excipients Compatibility Studies

Differential Scanning Calorimetery (DSC) DEE = (Pc / Tc) 100
The DSC measurements were performed on a Here, Pc is practical content,
differential scanning calorimeter with a thermal Tc is the theoretical content.
analyzer. All accurately weighed samples were
placed in sealed aluminum pans, before heating under X-ray Diffraction Studies (XRD)
nitrogen flow (20ml/min) at a scanning rate of 10 C X-ray diffraction analysis was performed using
min1 from 25 to 250 C. An empty aluminum pan Bruker axs diffractometer D 8Advanced model (high
was used as reference. beam monochromatic) using Cu radiation which was
generated at 40 Kv and 40 mA at 1.540600A. The
Drug polymer Interaction (FTIR) study rate of the scanning was 0.30C /min.
Fourier-transform infrared (FT-IR) spectra were
obtained by using shimadzu FTIR- 8400 Drug Content Determination
Spectrophotometer. The samples were previously ATR spherical agglomerates equivalent to 40 mg of
ground and mixed thoroughly with potassium ATR were accurately weighed, crushed and
bromide, an infrared transparent matrix, at 1:5 transferred to a 10 mL volumetric flask. To this, 50
(Sample/KBr) ratio, respectively. The KBr discs were mL of methanol was added and sample was sonicated
prepared by compressing the powders at a pressure of for 20 min so as todissolve the drug and the polymer.
5 tons for 5 min in a hydraulic press. The volume was made up to 100 mL withmethanol
and filtered through a 0.45 m filters. The filtrate was
Percentage Yield diluted withmethanol and analyzed at 246.5 nm by
The yield of microspheres was determined by uv-spectrophotometer.
comparing the whole weight of microspheres formed
against the combined weight of the copolymer and Solubility Study
drug. The apparent solubility of Spherical crystals of
Mass of microspheres obtained Atorvastatin calcium determined In water.Each
Percentage yield = X 100
Total weight of drug and polymer used
Spherical crystals in excess of drug equivalent to (40
mg) was added to 10 ml of solvent in glass vials with
Particle size and size distribution rubber closers. Then the vials were kept on a shaker
The microspheres were suspended in liquid paraffin incubator maintained at 37 0.5 C for 24 h. After
and examined using an optical microscope. Laser shaking, the vials were kept in an incubator at 37
diffraction technique (Malvern Instruments Ltd. 0.5 C for equilibrium for 10h. The solution was then
Malvern, UK) was used to study the size distribution filtered through 0.45 m Millipore, filtered and the
of the microspheres. The dispersant used was filtrate was assayed spectrophotometrically at 246.5
cyclohexane and the average particle size was nm.
calculated and expressed in microns.
In-vitro release studies
Drug Entrapment efficiency In-vitro dissolution studies were carried out with
The drug entrapment efficiency (DEE) was spherical agglomerates. Each test was carried out in
calculated by the following formula United States Pharmacopoeia dissolution apparatus II

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(Paddle) consisted of 900 ml , 0.1 N HCl maintained parameters,Bulk density,Tapped density, Hausner
at 37.0 0.5C and stirring at 75 rpm. An accurately ratio,Carrs index and Angle of repose.
weighed quantity of each sample equivalent to 40 mg
of Atorvastatin Calcium was subjected to the test. RESULTS AND DISCUSSION:
Samples 5 ml were withdrawn at predetermined time Differential Scanning Calorimetery (DSC)
interval (5, 10, 15, 20 & 30 minutes) and The pure drug Atorvastatin calcium shown as an
immediately replace with the equal volumes of endothermic peak at 189.14oC. The peak neither is
dissolution medium.. Diluted samples were analyzed nor shifted in the case of DSC of the Atorvastatin
at 246.5 nm by uv-spectrophotometer. calcium microspheres formulation containing
Atorvastatin calcium. The DSC of physical mixture
Flow Property of the Losartan Potassium showed an endothermic
Flowability of ATR and its spherical agglomerates peak at 189.14oC. The DSC spectra as shown in Fig
were determined in terms of the following 1 & 2.

Fig. 1: DSC of Atorvastatin calcium

Fig. 2: DSC of Atorvastatin calcium with Physical mixture

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Drug polymer Interaction (FTIR) study all characteristic peaks of Losartan potassium were
From the spectra Atorvastatin calcium and physical present in the combination spectrum, thus indicating
mixture of Atorvastatin calcium, it was observed that compatibility of the Losartan potassium and polymer.

Fig No.3: F IR of Atorvastatin calcium

Fig No.4: FTIR of Atorvastatin calcium Physical Mixture.

Table 2 Characteristics of Atorvastatin calcium microspheres

Formulation Percentage Yield Particle size(m) % Drug Content Entrapment
code MeanSD efficiency (%)

F1 45.0 1120.02 48.32 78.410.01

F2 50.0 1180.04 52.32 80.300.01
F3 64.1 1400.06 65.12 83.310.01
F4 80.0 1670.02 81.23 85.210.01
F5 90.83 1710.01 92.36 94.120.01
F6 85.0 1720.03 86.00 91.140.01
F7 91.5 1740.07 92.36 93.160.01

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SEM studies
The microspheres are almost spherical with smooth surface.

Fig 1: SEM photographs of Atorvastatin calcium microspheres

Table 3: In-vitro release studies

Time Percent drug release at time (hr)
(hrs.)
F1 F2 F3 F4 F5 F6 F7

1 50.200.9 49.20.6 44.310.3 46.210.9 43.210.6 42.130.3 43.120.2

3 55.100.3 54.210.2 53.200.9 52.410.4 51.230.5 49.210.5 48.320.2
6 60.010.34 59.010.1 57.230.3 56.140.3 55.320.4 54.250.5 53.230.1
9 68.870.32 63.020.69 61.350.2 60.540.1 59.240.2 58.360.5 56.320.2
12 75.580.7 67.580.6 63.210.7 62.300.5 61.250.2 68870.6 59.230.2
15 79.580.7 72.710.1 71.030.9 70.210.2 69.58.0.5 73.210.4 66.540.6
18 88.40.4 77.150.52 76.80.1 75.210.3 74.21 78.890.4 72.360.2
21 98.520.2 84.140.3 85.740.3 84.330.4 83.250.5 88.540.4 86.560.5
24 --- 91.230.2 92.690.5 91.360.3 89.720.3 98.310.4 93.360.3

In order to improve the release rate of drug from dissolution medium. Microspheres were prepared by
microspheres, 2.0 % w/v of camphor was included in the emulsion solvent evaporation method and
the formulations. The composition of the formulation evaluated. In vitro release studies for the prepared
is shown in Table 1. Camphor was dissolved in the microspheres were carried out .The release results are
polymer solution, its forms uniform distribution in shown in table 3. Formulation F6 showed better
the polymer solution. Upon microencapsulation the release rate than F7. The reason for this retarded drug
particles will be getting encapsulated by polymer release may be due to the hydrophobic nature of the
along with camphor. On drying due to volatile nature polymer, which prevents the penetration of the
camphor may get evaporated and forms pores on the dissolution medium into the microspheres leading to
surface of the microspheres, through which drug slower dissolution and diffusion of the drug
could easily diffuse to the aqueous phase or molecules from the microspheres.

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Table 5: Flow Properties of Losartan Potassium Microspheres

Formulation Bulk density Tapped density Compressibility Haussners Angle of repose

code (Avg. S.D.) (Avg. S.D.) index (Avg. ratio (Avg. (Avg. S.D.)
(Avg. S.D.) S.D.) S.D.)
F1 0.426 0.02 0.349 0.01 3.702 0.02 1.064 0.01 22.170 0.14
F2 0.232 0.01 0.389 0.03 4.349 0.03 1.059 0.01 21.120 0.17
F3 0.310 0.02 0.329 0.01 3.601 0.01 1.038 0.02 18.170 0.15
F4 0.416 0.01 0.355 0.02 3.875 0.01 1.040 0.01 20.140 0.12
F5 0.326 0.02 0.387 0.02 3.659 0.02 1.045 0.01 22.070 0.11
F6 0.327 0.02 0.431 0.01 3.071 0.02 1.087 0.01 21.210 0.18
F7 0.340 0.03 0.375 0.04 4.129 0.02 1.084 0.02 22.490 0.14

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