Formulation, optimization and in vitro evaluation of fast disintegrating tablets of salbutamol sulphate
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Date
2018-03
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Addis Ababa Universty
Abstract
Obstructive respiratory disorders include asthma and chronic obstructive pulmonary disorders characterized by airflow limitation. Salbutamol sulphate is widely used drug for the treatment of chronic obstructive airway diseases. Oral administration of SBS is complicated due to sore throat conditions, the patient experiences difficulty in swallowing a conventional tablet dosage form and more difficult to use inhalation devices effectively owing to advanced age and the presence of other comorbidities. Moreover, aerosol drug delivery needs inhalation technique and difficulty of swallowing conventional tablet dosage forms decreases patient compliance. This study provides FDTs of SBS formulation with lower disintegration times and good mechanical strength for an immediate release with rapid onset of action and better patient acceptance.
Formulation factors affecting the response variables (ammonium bicarbonate, crospovidone and microcrystalline cellulose to mannitol ratio (MCC/MNTL) were selected based on literature review and preliminary studies. Consequently, the levels of ammonium bicarbonate (subliming agent), levels of crospovidone (superdisintegrant) and MCC/MNTL (direct compression diluents) were considered. Ammonium bicarbonate level was fixed at 5% because of its esthetic impacts on tablets physical appearance. Central composite design was employed as study design to study and optimize the effect of formulation variables (concentration of crospovidone and MCC/MNTL) on tablet disintegration time, friability, hardness and wetting time. Accordingly, FDTs of SBS were prepared by sublimation technique with incorporation of superdisintegrant; and characterized for different tablet properties. Formulation (F6) containing 9.24% crospovidone, 1.25:1 MCC/MNTL and 5% ammonium bicarbonate showed the shortest disintegration time (12 ± 1.53 sec) and lowest wetting time (11 ± 1.00 sec) and; formulation (F8) containing 5% crospovidone, 2.31 : 1 MCC/MNTL and 5% ammonium bicarbonate had the largest crushing strength (7.88kg/cm2) and lowest friability (0.17%). These properties could be due to the disintegrant and binding properties of crospovidone and MCC respectively. All of the formulations released 75% of the label claim within 20 min.
Accordingly, ANOVA and lack of fit test obtained by Design-Expert illustrated that selected independent variables had significant effect on the response variables and excellent correlation were observed between actual and predicted values. Simultaneous optimization of the responses with desired attributes indicated disintegration time 14.2 sec, hardness 7kg/cm2 , friability 0.30
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and wetting time 13.2 sec at 7.82% crospovidone and 1.56: 1 MCC/MNTL (at 70%) as optimum formulation. The validity of an optimum formulation was further confirmed by the low magnitude of percent prediction error.
The optimized formulation was characterized for powder properties, tablets physicochemical properties and tablets morphology. The study showed that free flowing powder, robust prediction (between the actual and predicted values) and porous tablets. FDTs of SBS with lower DTs and good mechanical strength which is suitable for patients with obstructive respiratory disorders was successfully developed.
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Keywords
salbutamol sulphate, sublimation technique, superdisintegrant, fast disintegrating tablets, optimization, central composite design