Preparation and In Vitro Controlled Release Characteristics of Salbutamol Microcapsules by Coacervation Phase Separation Technique


D. Akiladevi1*, K. Elango2 and Sachinandan Basak3

1Department of Pharmaceutics, Mohamed Sathak A.J College of Pharmacy, Sholinganallur, Chennai-600119. 2Department of Pharmaceutics, Madras Medical College, Chennai-600003.      3Dr.Reddy’s Laboratories Ltd, Bachupalli, Qutubullapur, RR district 500090, Andhra Pradesh.

*Corresponding Author E-mail:



Salbutamol microcapsules were prepared by coacervation – phase separation method using ethylcellulose as polymer. Three formulations of microcapsules were prepared in the drug to polymer ratio of 1:5, 1:4 and 1:3 and were evaluated for its drug content, Particle size determination and in vitro release behavior using potassium chloride buffer of pH 2 up to 8hrs and 30min. All the formulation (F1, F2 and F3) showed uniformity in drug content, sieve analysis results indicated that major portion of microcapsules were in the range of 350-700µm.The in vitro studies revealed that F2 showed better controlled release compared to other formulations up to 8hrs and 30min.The drug release from the matrix and that of marketed product was found to be diffusion controlled by means of the swelling of drug loaded microcapsules. It was concluded that Salbutamol can be effectively microencapsulated using ethylcellulose by coacervation – phase separation technique.


KEYWORDS: Salbutamol, microcapsules, in vitro controlled release, coacervation phase separation




Microcapsules developed for use in medicine consists of core material (drug), which are coated with a coating material consisting of a mixture of a film forming polymer derivative, a hydrophobic plasticizer, a functional agent and a nitrogen containing polymer. Microencapsulation1,3 involves the preparation of microparticles having the size range of 1-2000µm. Microcapsules are often called by other terms like coated granules, pellets, seeds, micro spherules, and spansules. Microparticles are produced for protection of core material, reduction of gastric irritation, decrease in volatility, conversion of liquid, to pseudo solid, cell micro encapsulation peptide and protein delivery and for designing pulsatile drug delivery systems2. These provide controlled or sustained drug delivery systems and effectual drug therapies. The potential advantages of microencapsulation technique lies in the fact that in this technique the coating is done to the smallest particle, due to this drug moieties can be widely distributed throughout the GI tract thus it potentially improves drug absorption4,5.


Salbutamol (Albuterol) is a β2 agonist used in treatment of asthma. It is a bronchodilator and readily absorbed from gastrointestinal tract and its biological half life is 4-6 hrs6-9.


Ethyl cellulose is soluble is nontoxic biocompatible, non biodegradable polymer which is soluble in wide variety of solvents that nearly have same cohesive energy or density or solubility. The lower molecular weight aliphatic esters and ketones yield ethyl cellulose of low viscosities with good strength and extensibility10-11. The aim of the present work is to encapsulate salbutamol using ethyl cellulose polymer of different ratios 1:5, 1:4, 1:3 by coacervation phase method to provide a sustained release formulation of salbutamol. Their drug content was estimated and the in vitro dissolution drug release was evaluated in potassium chloride buffer of pH 2.



i) Materials required:

Salbutamol was received as a gift sample by Zydus Cadila Healthcare Ltd. Ethyl cellulose was supplied by M/s Sun Pharmaceuticals, Baroda, India. Electric stirrer with provision for speed regulation, mandle, USP Dissolution apparatus (basket type) were obtained from technical lab products. All other materials were used of analytical grade.


ii) Method of preparation of microcapsules:

Required amount of drug and polymer were weighed for the three ratios of drug: polymer (1:5, 1:4, 1:3). Ethyl cellulose was dissolved in 100ml of cyclohexane at 80°C with constant stirring. The drug was added gradually with vigorous stirring at a constant speed. The temperature was reduced to 20°C.The microspheres formed were filtered, washed with solvent, dried and weighed.

iii) Calibration curve:

50mg of the drug was dissolved in 500ml using potassium chloride buffer. From this stock solution 10, 20,30,40,50,60,70,80 and 90ml were taken and made up to 100ml in standard flasks.10ml samples was taken from each and analyzed spectrophotometrically at 276nm.The mean absorbance readings of salbutamol in potassium chloride buffer was illustrated in table1 and the standard curve was shown in fig-1.


Table No.1 Mean absorbance readings of Salbutamol

SI. No

Concentration (µg/ml)

Absorbance at 276nm

Potassium Chloride buffer (pH 2)


























iv) Assay of Salbutamol:

The drug was extracted from ethyl cellulose microcapsules. Using toluene as solvent for ethylcellulose. When the entire ethyl cellulose had dissolved in toluene; the drug was extracted in measured volume of water and analyzed spectrophotometrically at 276nm.


Fig-1 Standard curve for Salbutamol


Series 1: Potassium chloride buffer (pH 2)


v) In vitro drug release study:

The in vitro dissolution studies for all formulations of salbutamol were conducted at pH 2.0 using potassium chloride buffer solution and the results shown in Table No.2 were mean of the triplicate values with S.D. The in vitro drug release profile of salbutamol was shown in Fig.2. The basket type dissolution apparatus was used and the speed was maintained at 100rpm. The temperature was maintained at 37 C ± 2 C. Samples collected at intervals of half an hour were analyzed.


Table No.2 In vitro dissolution of Salbutamol microcapsules

Time in hours

%  Cumulative drug release ± S.D




Marketed Product


33.02 ± 0.175

24.75 ± 0.135

33.78 ± 0.165

30.16 ± 0.132


36.36 ± 0.258

29.42 ± 0.233

40.91 ± 0.421

45.12 ± 0.165


38.03 ± 0.308

34.57 ± 0.380

44.04 ± 0.321

46.23 ± 0.187


41.59 ± 0.302

39.12 ± 0.314

57.49 ± 0.331

58.23 ± 0.233


42.13 ± 0.198

42.96 ± 0.138

59.22 ± 0.198

59.16 ± 0.316


44.22 ± 0.233

45.11 ± 0.233

62.40 ± 0.321

61.23 ± 0.285


49.47 ± 0.374

48.56 ± 0.371

64.74 ± 0.194

63.85 ± 0.211


53.66 ± 0.368

52.81± 0.121

67.86 ± 0.264

68.23 ± 0.321


65.79 ± 0.184

54.65 ± 0.244

70.94 ± 0.301

71.58 ± 0.250


78.22 ± 0.308

58.30 ± 0.234

74.92 ± 0.193

73.69 ± 0.330


84.80 ± 0.412

69.51 ± 0.326

76.54 ± 0.222

75.13 ± 0.112


Fig-2 In vitro dissolution study



Three formulations of microcapsules were prepared in the ratio of 1:5, 1:4, 1:3. Formulation processes were the same for all formulations of drug-loaded microcapsules. All the formulations showed drug content of 97-102%. The invitro release of microcapsules that are prepared in the ratio of 1:5, 1:4, and 1:3 showed the percentage cumulative release of 84.8%, 69.51%, and 76.54% respectively at the end of 8 hours 30 minutes. Based on the result F2 showed better controlled release profile than other formulations.



Microcapsules were prepared by coacervation phase separation method using cyclohexane as a solvent and ethyl cellulose as a coating material. It was found that concentration of polymer altered the release rate of drug.



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Received on 29.09.2010          Modified on 20.10.2010

Accepted on 26.10.2010         © RJPT All right reserved

Research J. Pharm. and Tech. 4(2): February 2011; Page 276-278