**4.1 Fourier Transform infrared spectroscopy (FTIR)**

Fourier transform infrared analysis will be performed to detect any changes in chemical constitution of the drug after combining it with the excipients. Fourier transform infrared analysis will be performed to detect any interaction between the drug and ammonium bicarbonate and crospovidone. The compatibility between the drug and excipients used in many formulations is being studied using Fourier transform infrared spectroscopy (FTIR) at room temperature. Samples of drug and excipients and physical mixtures of both are commonly grinded and mixed thoroughly with KBr. at a 1:5 sample/KBr ratio. The KBr discs were prepared by compressing the powders at a pressure of 5 T for 5 min in a hydraulic press. The scanning range was 400 to 4000 cm−1and the resolution was 8 cm−1.

#### **Figure 1.**

*The differential scanning calorimetric thermograms and thermogravimetric analysis of salbutamol (A) and salbutamol and crospovidone physical mixture (B).*

#### **4.2 Powder X-ray diffraction**

X-ray powder diffraction (XRD) is a rapid analytical technique primarily used for phase identification of a crystalline material and is a unique method in determination of crystallinity of a compound. XRD will be performed to detect any crystallinity between the drug and ammonium bicarbonate and crospovidone. The powder X-ray diffraction patterns were measured using an X-ray diffractometer with Cu anode material. The diffraction pattern was measured with a voltage of 40kV and a current of 15 mA in the area of 0° <2Theta <100°.

#### **4.3 Differential scanning calorimetry (DSC)**

DSC is one of many types of thermal analysis techniques useful for characterizing pharmaceutical solids. Calorimetry is quite useful to measure chemical reactions such as cross-linking or curing reactions, oxidation processes, and thermal decomposition. Chemical reactions and the kinetics of these reactions under either inert or reactive atmospheres can be quantified nicely. DSC will be performed to detect any thermal decomposition between the drug and excipients. The thermal behavior can be estimated using differential scanning calorimetry by using Indium as a standard to calibrate the differential scanning calorimetry (DSC) temperature and enthalpy scale. The samples are hermetically sealed in aluminum pans and heated at a constant rate of 10°C/min, over a scanning temperature range of 0–400°C. An inert atmosphere was maintained by purging with nitrogen at a flow rate of 100 mL/min.

The DSC graphs of salbutamol sulfate and salbutamol sulfate and crospovidone physical mixture are presented in **Figure 1A** and **B**, respectively The DSC curve of the pure drug showed a sharp endothermic melting peak with the onset of about 210°C reaching maximum at 288°C. The DSC curve of salbutamol sulfate and crospovidone physical mixture showed a sharp endothermic melting peak with the onset of about 210°C reaching maximum at 283° C due to polymorphs (R) – salbutamol; as salbutamol sulfate exists in racemate forms S and R [45]. Besides, the small difference in the decomposition temperature could be associated with the different crystal morphology of the polymorphs [46, 47]. The thermogram of the corresponding physical mixture showed small endothermic peak indicating that amorphous form existed in the physical mixture which is in agreement with PXRD results. These might explain the faster dissolution of the drug in the physical mixture [26]. Thermogravimetric analysis (TGA) has been performed for the blends, and the weight loss due to the volatilization of the degradation products has been monitored as a function of temperature [48] as shown in **Figure 1A** and **B**, respectively [49]. Temperature at the maximum rate of weight loss (Tmax) improvement of salbutamol sulfate is ascribed to the compatibility of salbutamol sulfate and crospovidone in blends.
