Formulation and Evaluation of Salbutamol Sulphate Taste Masked Oral Disintegrating Tablets

Salbutamol is a short acting, selective beta2-adrenergic receptor agonist used in the treatment of astama and COPD. The aim of this study is to formulate oral disintegrating tablets of salbutamol sulphate to achieve rapid dissolution, absorption and further improving the bioavailability of the drug. Oral disintegrating tablets of salbutamol sulphate were designed with a view to enhance the patient compliance and provide a quick onset of action. The oral disintegrating tablets were prepared by using different synthetic polymers by direct compression method. Development of the formulation in the present study was based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution. A fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablets was found to be 14.39-32.41 sec and the drug content of tablets in all formulations was found to be between 87.48-99.96 %, which complied within the limits established in the Indian pharmacopeia. The study concluded that taste of the drug was masked with the help of sodium saccarhin, flavor and the concentration of super disintegrating agent increases the disintegration time of tablets get decreases. The formulation (F9) had a minimum disintegration time of 14.39 sec and 99.96 % of the drug was released within 20 min.

Formulation, Optimization and In Vitro Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate using a Combination of Superdisintegrant and Subliming Agent

Aim: The present research work was aimed to formulate fast disintegrating tablets (FDTs) of salbutamol sulphate (SBS) using a combination of superdisintegrant and subliming agent, optimize the formulation and evaluate the in vitro performance of the developed FDTs. Materials and Methods: A formulation of SBS FDT was developed using a combination of superdisintegrant – crospovidone and subliming agent – ammonium bicarbonate (AB) in which formulation variables, namely levels of crospovidone and microcrystalline cellulose (MCC):Mannitol (MNTL) ratio were evaluated for their effects on the response variables - disintegration time, hardness, friability and wetting time of the resulting FDTs. By employing a central composite design (CCD) methodology, the FDTs were optimized to achieve optimum levels of the formulation factors. Results: The desired optimum condition was obtained at 7.82% crospovidone and 70% of 1.56:1 MCC: MNTL ratio while maintaining AB at 5% level for aesthetic reasons. Under the optimized conditions, the disintegration time, hardness, friability and wetting time were 14.57±0.53 sec, 7.17±0.82 kg/cm2, 0.311% and 13.14±0.69 sec, respectively. The experimentally observed responses were found to be in close agreement with the predicted values for the optimized formulation. Moreover, the validity of the obtained optimal point was confirmed by the low magnitude of percent prediction error (<5%). Conclusion: FDTs of SBS were successfully formulated and optimized using CCD employing a combination of superdisintegrant and subliming agents.

Repurposing Melt Degradation for the Evaluation of Mixed Amorphous-Crystalline Blends

Medicine regulators require the melting points for crystalline drugs, as they are a test for chemical and physical quality. Many drugs, especially salt-forms, suffer concomitant degradation during melting; thus, it would be useful to know if the endotherm associated with melt degradation may be used for characterising the crystallinity of a powder blend. Therefore, the aim of this study was to investigate whether melt-degradation transitions can detect amorphous content in a blend of crystalline and amorphous salbutamol sulphate. Salbutamol sulphate was rendered amorphous by freeze and spray-drying and blended with crystalline drug, forming standards with a range of amorphous content. Crystalline salbutamol sulphate was observed to have a melt-degradation onset of 198.2±0.2°C, while anhydrous amorphous salbutamol sulphate prepared by either method showed similar glass transition temperatures of 119.4±0.7°C combined. Without the energy barrier provided by the ordered crystal lattice, the degradation endotherm for amorphous salbutamol sulphate occurred 50°C below the melting point, with an onset of 143.6±0.2°C. The enthalpies for this degradation transition showed no significant difference between freeze- and spray-dried samples (p>0.05). Distinct from convention, partial integration of the crystalline melt-degradation endotherm was applied to the region 193–221°C which had no contribution from the degradation of amorphous salbutamol sulphate. The linear correlation of these partial areas with amorphous content, R2=0.994, yielded limits of detection and quantification of 0.13% and 0.44% respectively, independent of drying technique. Melt-degradation transitions may be re-purposed for the measurement of amorphous content in powder blends, and they have potential for evaluating disorder more generally.

DETERMINATION OF PROCESS RELATED GENOTOXIC IMPURITIES OF SALBUTAMOL SULPHATE BY LC METHOD

The main aim of this research work is to develop a suitable LC method for the quantitative determination of genotoxic impurities contains in Salbutamol Sulphate which is coming from the chemicals used during the manufacturing process. In manufacturing process many unwanted chemical materials are being used and out that many are following under Genotoxic category. After screening and doing the assessment on the genotoxic predication in salbutamol sulphate. The possible genotoxic impurities identified and likely to present in salbutamol Sulphate as Salicylic acid,[1][2][3] Acetyl methyl Salicylate (AMS),[4][5][6] Benzyl methyl salicylate (BMS),[7] Bromo-compound[8] and Dibromo-compound[8]. The main challenge is to separate all impurities from each other to get better resolution and response. As genotoxic[19][24] impurities estimation limit in final molecule is very minute and low it is not easy to quantify at ppm level present in Salbutamol sulphate in Active Pharmaceutical Ingredients. Hence the LC method was developed on Waters HPLC system (Water’s Ltd, USA) with 2995 UV detector at 273 nm as wavelength and 1.0 ml/min flow rate by using Spherical end-capped octylsilyl silica gel for chromatography (l = 0.15 m, Ø = 4.6 mm, 3µm) long with gradient system. The chromatographic and integrated data were recorded using Empower -3 data acquisition software. The limit of detection and the limit of quantitation for the impurity were established. Validation of the developed LC method was carried out as per ICH requirements and the data shows that the proposed method is specific, linear, accurate, precise and robust. This method has been tested in a number of Salbutamol Sulphate and used successfully for quantification of the reported impurities at ppm level. The developed LC method was found to be suitable to quantify the genotoxic impurities Salicylic acid, Acetyl methyl Salicylate (AMS), Benzyl methyl salicylate (BMS), Bromo-compound and Dibromo-compound at ppm level present Salbutamol Sulphate.

Concurrent analysis of ambroxol HCl and salbutamol sulphate from tablet formulation by RP-HPLC

RP-HPLC method was developed for concurrent analysis of ambroxol HCl and salbutamol sulphate from tablet formulation. Analytes were separated with mobile phase consisting of mixture of methanol and water (0.1% triethylamine) in the ratio 50: 50 at a flow rate of 0.7 ml/min with Nucleosil (4.6 mm I.D x 250 mm) C18 column. The retention time of ambroxol HCl and salbutamol sulphate was found to be 3.61 and 6.20 min, respectively. The detection was carried out at 224 nm. The dynamic range for ambroxol HCl and salbutamol sulphate observed was 15-75 µg/ml and 1-5 µg/ml, respectively. The percent recovery obtained for ambroxol HCl and salbutamol sulphate were close to 100%. Obtained statistical data of results was found to satisfactorily.

Simultaneous estimation of salbutamol sulphate and ambroxol HCl from their combined dosage form by UV-VIS spectroscopy using simultaneous equation method

A simple UV-Vis Spectrophometric method was developed for the simultaneous determination of salbutamol sulphate and ambroxol HCl (AMB) from their combined dosage form. The method employs formation and solving of simultaneous equation using 242 nm and 272 nm as two analytical wavelengths (λMax of the drugs) of detection. Both the drugs obeyed Beer-Lambert’s law over the concentration range 1-50 μg/mL for salbutamol sulphate and 10-50 μg/mL for ambroxol HCl, respectively. The developed method was validated for Accuracy, Precision, Limit of Detection and Limit of Quantification as per ICH guidelines and results of analysis were validated statistically.

The Use of a Three-Fluid Atomising Nozzle in the Production of Spray-Dried Theophylline/Salbutamol Sulphate Powders Intended for Pulmonary Delivery

The aim of this study was to investigate the use of a three-fluid atomising nozzle in a lab-scale spray dryer for the production of dry powders intended for pulmonary delivery. Powders were composed of salbutamol sulphate and theophylline in different weight ratios. The three-fluid nozzle technology enabled powders containing a high theophylline content to be obtained, overcoming the problems associated with its relatively low solubility, by pumping two separate feed solutions (containing the two different active pharmaceutical ingredients (APIs)) into the spray dryer via two separate nozzle channels at different feed rates. The final spray-dried products were characterized in terms of morphology, solid-state properties and aerosolization performance, and were compared with an equivalent formulation prepared using a standard two-fluid atomising nozzle. Results confirmed that most of the powders made using the three-fluid atomising nozzle met the required standards for a dry powder inhaler formulation in terms of physical characteristics; however, aerosolization characteristics require improvement if the powders are to be considered suitable for pulmonary delivery.