Ethylcellulose, a nonbiodegradable and biocompatible polymer, one of the extensively studied encapsulating materials for the controlled release of pharmaceuticals, was selected as the retardant material for Propranolol hydrochloride. Ethylcellulose, a polymer to microencapsulate a drug by coacervation phase separation technique, emulsion solvent evaporation technique, and spherical crystallization technique [
The highly water soluble drug, Propranolol HCl, was gift samples from Micro Advanced Research Center, Pvt. Ltd., Bangalore, and used as a model drug. The nonbiodegradable polymer, Ethylcellulose (300 cps) was purchased from Sigma Eldritch, USA. The two biodegradable polymers, Eudragit RS and Eudragit RL, were donated by Colorcon Asia Pvt. Ltd., Goa. Acetone, isopropane, and N-Hexane were from Merck Specialities Pvt. Ltd., Mumbai. Heavy liquid paraffin, potassium dihydrogen phosphate, and sodium hydroxide were procured from S.D. Fine Chemicals, Mumbai, India.
Polymeric microparticles were prepared by dispersing accurately weight quantities of Propranolol hydrochloride and polymers individually (Ethylcellulose 300 cps, Eudragit RS 100, and RL 100) in the primary phase as a solvent (1 : 1 combination of acetone and isopropanol) with continuous stirring at 500 rpm by using magnetic stirrer for 15 min. Sustained released microparticles of drug were prepared by modified hydrophobic emulsion solvent evaporation method (O/O) [
The diameter of microparticle of each formulation was measured by spreading a thin layer of microparticles on a glass slide and viewing the microparticles under an optical microscope fitted with an eyepiece having 40x to 100x resolution of Motic microscope (B1 series, Motic, China). Each sample was measured at three times and an average particle size was articulated as mean diameter.
The encapsulation efficiency of the prepared microparticles was determined by accurate weighing and added in acetone to dissolve polymer and then add the required volume of distilled water. Precipitate solution was filtered and make up the volume up to 100 mL into a volumetric flask. Recovered filteration was measured at maximum absorbance at 289 nm by using UV-visible spectrophotometer (UV-1800 Shimadzu Co. Ltd., Japan) and encapsulation efficiency was calculated using the following equation:
IR spectra of pure drug and microparticles prepared by using polymers like Ethylcellulose, Eudragit RS, and Eudragit RL-loaded microparticles were obtained with infrared (IR) spectra of the samples that were scanned in the range from 400 to 4000
The surface morphology of microparticles was analyzed by scanning electron microscopy (SEM). The microparticles were fixed with carbon-Glu and coated uniformly with gold palladium under argon atmosphere. Samples were then observed with a Hitachi model S4800, Japan, scanning electron microscope.
The
In the present paper, Ethylcellulose (300 cps) polymer has higher viscosity grade compared with polymethacrylate resins polymers like Eudragit RS 100 (RS) and RL 100 (RL). These are two copolymers synthesized from acrylic and methacrylic acid esters, containing a low level of quaternary ammonium groups. RS has a lower content of charged groups (4.5–6.8%), and it is considered less permeable to water with respect to the more readily permeable RL (8.8–12% ammonium groups) [
Batch yield, entrapment efficiency, drug content, and size of prepared microparticles.
Polymer grade | Code | Ratio | % yield | Encapsulation efficiency | Drug content | Particle size ( |
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EC 300 | F1 | 1 : 1 |
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F2 | 1 : 3 |
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F3 | 1 : 5 |
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F4 | 1 : 7 |
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RS 100 | F5 | 1 : 1 |
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F6 | 1 : 3 |
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F7 | 1 : 5 |
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F8 | 1 : 7 |
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RL 100 | F9 | 1 : 1 |
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F10 | 1 : 3 |
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F11 | 1 : 5 |
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F12 | 1 : 7 |
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The obtained results concluded that the fact that the particle sizes were directly proportional to polymers concentration may be due to increase in viscosity of the internal phase, and inversely proportional the surfactant concentration may be due to the formation of new surfaces for the small emulsion globules. Formulation prepared using Ethylcellulose 300 cps showed higher encapsulation efficiency (96.7 ± 0.5) than those prepared using Eudragit RS 100 (83.7 ± 0.6) and RL 100 (89.7 ± 0.6). It was also found that release of drug is slower than formulation prepared from Eudragit polymers. Formulations F4, F6, and F12 which are prepared using higher drug to polymer ratio with 0.4% surfactant concentration showed drug release of 59.08 ± 0.2, 75.10 ± 0.4, and 92.9 ± 0.3 percent, respectively, at 12 h. All recovered microparticles were spherical in shape and slightly porous in nature (Figure
Surface morphology of recovered microparticles.
Drug polymer interaction was determined by comparing the IR spectra of Propranolol hydrochloride loaded Ethylcellulose microparticles with the IR spectrum of pure drug.
As shown in Figure
FTIR Spectra.
Figure
Release profile of Propranolol hydrochloride from some selected formulations.
The formulation F4 was more sustained than formulations F8 and F12, because the maximum number of particles may extend the time to release the drug from F4 formulation. In F4 formulation prepared by using Ethylcellulose polymer and 0.4%, v/v span 80 surfactant was used which gives larger size particles than F8 and F12 formulation. At the end of 12 hours F4 formulation released 59.08 ± 0.2, F8 released 75.10 ± 0.4, and F12 released 92.9 ± 0.3 percent propranolol hydrochloride. Drug bursts at the first hour of the formulations F4, F8, and F12 are 42.8 ± 0.4, 53.9 ± 0.4, and 63.8 ± 0.4, respectively; it may be due to the drug present at the surface of particles. The burst release effect may be due to the adsorption of the drug on the surface of the particles or due to concentrating the drug at the surface of the particles because insufficient concentration or ineffectual surfactant was unable to encapsulate drugs at the core of particles and drug moved towards the interface of both phases. The release kinetics of all selected formulations is explained in Table
Formulation code |
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Zero order | First order | Higuchi | Hixon-Crowell | |
F4 | 0.8744 | 0.9046 |
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0.8953 |
F8 | 0.9657 | 0.9828 |
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0.9793 |
F12 | 0.9870 | 0.9783 |
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0.9929 |
Formulations F4, F8, and F12 all show Higuchi model. It describes the release of drugs from an insoluble matrix as a square root of time dependent process based on Fickian diffusion [
In Higuchi or square root kinetics, drug diffuses at a comparatively slower rate as the distance for diffusion increases. From all above evaluations, it was concluded that the prepared microparticles were successfully sustained for 12 h. Thus from all these results it was discovered that Ethylcellulose 300 cps viscosity range polymer can be used to formulate sustained release microparticles at different ratios.
From the above results, it was concluded that Propranolol hydrochloride was successfully encapsulated into Ethylcellulose and Eudragit microparticles using O/O hydrophobic emulsion solvent evaporation method. Span 80 was more suitable surfactant with a concentration of 0.4%, v/v. The 1 : 7 drug-polymer ratio obtained the highest encapsulation and sustained the propranolol hydrochloride for 12 h. It follows Higuchi model release kinetics; therefore this dosage form maintains the drug level in therapeutic window which may help to minimize the side effects and minimize the frequency of dose which improve patient compliance.
There is no conflict of interests regarding the publication of this paper.
The authors are very much thankful to the University Grant Commission, New Delhi, for granting financial support for this valuable research work and Micro Advanced Research Center, Pvt. Ltd., Bangalore, for providing gift sample of Propranolol hydrochloride as well as Colorcon Asia Pvt. Ltd., Goa, for Ethylcellulose polymer.