Journal of Pharmacy And Bioallied Sciences

: 2012  |  Volume : 4  |  Issue : 5  |  Page : 71--73

Formulation and evaluation of multiparticulate system for chronotherapeutic delivery of salbutamol sulphate

M Pallavi Chaudhari1, D Pravin Chaudhari2,  
1 Pad. Dr. D. Y. Patil College of Pharmacy, Near Z.S.I, Sector 29, Akurdi, India
2 Modern College of Pharmacy, Sector 21, Yamunanager, Nigdi, Pune, India

Correspondence Address:
M Pallavi Chaudhari
Pad. Dr. D. Y. Patil College of Pharmacy, Near Z.S.I, Sector 29, Akurdi


Solution layering technique was used to prepare pellets of Salbutamol Sulphate. A multiparticulate system was prepared with pH independent and pH dependent coatings, and evaluated as pulsatile drug delivery system. Salbutamol sulphate release was studied from methacrylate coated pellets from non pareils. Morphology was studied using Scanning Electron Microscopy for the characterization of prepared pellets. Combination of Eudragit RSPO (pH independent) and Eudragit L100 (pH dependent) was used for coating of the pellets. Different concentrations of this polymeric combination were loaded on to the drug-loaded pellets. The aim of this study was to investigate the effect of physicochemical properties of the polymers on the release profile of Salbutamol sulphate from the pellets dosage form. The in-vitro study suggested that Eudragit RSPO and Eudragit L100 at 10% coating level led to an optimum pulsatile release behavior. The coated pellets prepared by solution layering technology successfully released drug after specific lag time indicating pulsatile drug delivery. It was revealed that Eudragit RSPO has the effect to retard drug release. The results generated in this study showed that proper selection of polymeric materials based on their physicochemical properties is important in designing pellets dosage form with suitable dissolution profile.

How to cite this article:
Chaudhari M P, Chaudhari D P. Formulation and evaluation of multiparticulate system for chronotherapeutic delivery of salbutamol sulphate.J Pharm Bioall Sci 2012;4:71-73

How to cite this URL:
Chaudhari M P, Chaudhari D P. Formulation and evaluation of multiparticulate system for chronotherapeutic delivery of salbutamol sulphate. J Pharm Bioall Sci [serial online] 2012 [cited 2022 Jul 7 ];4:71-73
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Full Text

Pulsatile drug delivery systems (DDS) are characterized by a rapid drug release after a predetermined lag time and can be classified as single unit (e.g. tablet or capsule) or multiparticulate (e.g. pellets) systems. [1] Pellets offer advantages like free flowing, flexibility in design, spherical shape and low surface area to volume ratio of pellets help in uniform film coating. [2],[3] The layering process is the process in which drug in powder, solution or suspension form is layered onto seed materials. [4]

 Materials and Methods

Salbutamol sulphate was obtained from Scortis Labs (P) Ltd, Jaipur, India. Eudragit RSPO and Eudragit L100 (Rohm Pharma GmbH, Darmstadt, Germany), Non-pareil seeds were gifted from Micropellet (Nashik), all other chemicals were of reagent grade.


Preparation of Salbutamol sulphate pellets by Solution Layering Technology-Solution of Salbutamol sulphate and PVP K-30 in IPA-water mixture (80:20) was sprayed onto the rotating nonpareil seeds in 8" diameter coating pan.PVP K30 was used as binder. The flow rate of solution was maintained constant at 1 ml/min, which prevents the agglomeration of pellets during coating process. The inlet air temperature was 45°C and the drying time after each application was 2 min. The speed of coating pan was 25 rpm.

Formation of coating layer

The drug loaded beads were coated with polymer solution of different concentrations from F1 toF5 (100:0, 70:30, 50:50, 30:70 and 0:100) at the flow rate of 1ml/min. The solution was plasticized by TEC (10%, w/w based polymer mass) and Talc also was added as antisticking agent (5% (w/w) related to dry polymer). The processing conditions were as follows: Inlet air temperature was 45°C and the drying time after each application was 2.5 min. Pan speed 25 rpm and atomizing pressure was 2 lb/inch 2 . Samples taken periodically throughout a run to give desired weight gain of 5%, 10% and 15% (w/w) respectively. All pellets were stored in plastic bags at room temperature until required.

Evaluation of pellets


Friability of pellets was determined by subjecting 10 g of pellets in (Roche friabilator) at 4 min at 25 rotation/min. The abraded samples were sieved and the pellets retained on the sieve were weighed and percent friability was calculated from the difference in the weight of the pellets before and after friability.

Flow properties

The Carr compressibility index and Hausner ratio of the coated pellets were computed on the basis of tapped density and poured bulk densities.

Drug content

Required drug loaded pellets were ground into fine powder and all the powder was transferred into 100 ml volumetric flask and dissolved in 100 ml distilled water. Samples were taken, filtered, diluted suitably and assayed spectrophotometrically at 276 nm. The experiment was performed in triplicate and mean values were taken.

Scanning electron microscopy (SEM)

Scanning electron microscopy was performed to characterize the surface of the formed pellets. SEM photographs [Figure 1] of the methacrylate coated nonpareil pellets were taken before and after coating using (JEOL 5400, Japan) Scanning microscopy. The coated pellets were loaded on studs and applied fine gold coating with gold for 5 min at 10 mA ion current under a pressure of 0.1 Torr using ion sputter. The coated pellets were scanned and the micrographs were examined.{Figure 1}

In vitro drug release

Release studies were performed in dissolution apparatus (VEEGO Model) tests were conducted in 900 ml of dissolution medium maintained at 37±0.5°C with a basket rotation speed of 50 rpm. The pH of the medium was varied over the course of the experiment: 0.1N hydrochloric acid (pH 1.2) was used for the first 2 h followed by phosphate buffer pH 6.8 for rest of the time. Samples 5 ml were withdrawn at predetermined times and analyzed at 276 nm by UV Spectrophotometer (Shimadzu 1700).

Fourier transform infrared spectroscopy

The infrared (IR) spectrum of the coated pellets was compared with that of Salbutamol sulphate to confirm the chemical integrity of the drug in the formulations developed. The samples were powdered and mixed with dry powdered potassium bromide. The powdered mixture was taken in sampler and scanned in FTIR spectrophotometer (Jasco, FT/IR 4100)

 Results and Discussion

The friability was below 1%, indicating that the pellets produced were sufficiently hard to withstand coating process. Bulk density of the coated pellets increased harmonically along with polymer load which reflects that volume of the pellets might not be increased proportionally along with increase in weight of pellets due to polymer load. The drug content was found to be in the range from 94.60±0.01% to 98.27±0.012%. SEM photographs of optimized formulation [Figure 1], [Figure 2] and [Figure 3] it was observed that coating was even on the pellets and it was also observed that pellets appeared smooth and showed good adhesion. The pellets with 5% coating level failed to show sufficient retardation and drug release. It indicates that 5% polymer load is not enough to coat around the pellets uniformly to get the desired effect. Pellets were coated with the 10% coating level of only Eudragit RSPO (100:0, F1) initial drug release was less and later drug release increased up to 4.5 hours and increased linearly from 5 th hour to 8 th hour. Eudragit RSPO provides less pores and channels for the effective drug diffusion resulting in lower drug release. Whereas, For F5 (0:100) formulation, it was observed drug release get increased. For F2, drug release increases as compared to F1.Pellets coated with (50:50 ratio, F3), drug release was increased linearly due to combined effect of the high permeability of the Eudragit L100 and low permeability of Eudragit RSPO. The drug release from the system using Eudragit RSPO:L100 (30:70, F4) polymeric membrane was linear with the time. Eudragit L100 has a pH-dependent solubility and its swelling and erosion increase as the pH increases. As expected, the release rate decreased with increasing coating level (15%), due to the increased diffusion pathways. But, the release was too retarded as compared to 10% coating level, so did not show the required results. Thus from the drug release studies, each profile shows a typical sigmoidal pattern that is characterized by a distinctive lag-time followed by a rapid drug release and formulation F4 (30:70, at 10% coating level), [Figure 4] showed require release rate in comparison with other formulations. Thus, this study clearly indicated that the 30:70 ratio at 10% coating level is more suitable among the polymers combinations used in the formulations to design pulsatile release formulations of Salbutamol sulphate for 8 hours. IR studies showed compatibility of the coated pellets with drug.{Figure 2}{Figure 3}{Figure 4}


Solution layering technology has been successfully utilized to develop, reproducible, controlled release chronotherapeutic dosage form of Salbutamol sulphate. The release profile of drug was found to be a function of coating level as well as the physico-chemical nature of the polymeric materials. It was concluded that Formulation F4 (30:70, 10% weight gain) was good formulation as it was meeting all specifications for angle of repose, friability test, drug content and drug release.


The authors wish to thank Scortis Labs (P) Ltd, Jaipur, for gift sample of Salbutamol sulphate. Authors are also thankful to Modern College of Pharmacy for providing the help during this work.


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