Compatibility Studies Between Gatifloxacin and Pharmaceutical Excipients through Differential Scanning Calorimetry and Infra Red Spectroscopy

 

Rajendra Jangde1*, Rahul Singhour2 and SJ Daharwal1

1University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010 India

2Aristo Pharmaceutical Mandideep, Bhopal (M.P.), India

 

ABSTRACT:

Proper formulation is an important aspect of any dosage form design. FT-IR and Differential scanning calorimeter were used to evaluate the compatibility of Gatifloxacin and selected Excipients used in the development of suspensions formulation. In the first phase of Differential scanning calorimeter was used in the any interaction. In the next phase, excipients defined as prototype formula were tested for their compatibility with Gatifloxacin. Based on the results, methyl paraben and polyvinyl pyrrolidone were found show interaction with Gatifloxacin. Results of Differential scanning calorimeter and FT-IR demonstrated incompatibility between Gatifloxacin and MethylParaben. All the excipients defined in the prototype formula were found to be compatible with Gatifloxacin. Using the Excipients that were found to be compatible with Gatifloxacin. FT-IR and Differential scanning calorimetry was used to investigate the physicochemical compatibility between Gatifloxacin and various used in suspension manufacturing. The Gatifloxacin found to be compatatible with polyvinyl alcohol and acacia. Although interactions of Gatifloxacin with methyl paraben, polyvinyl pyrrolidone were observed. It cannot be conclusive stasted that interactions incompatibility will occur during storage at room temperature.

 

KEYWORDS: Gatifloxacin, FTIR, differential scanning calorimetry, Pharmaceutical excipents, preformulation compatibility.

 

INTRODUCTION:

The successful formulation of a stable dosage form depend on careful selection of the excipients used to make administration easier or more suitable, improve patient compliance, promote release and bioavailability of the drug and protect it from degradation1.The development of pharmaceutical formulations requires previous knowledge of the physicochemical properties of the drug , excipients and analytical instrumentation that can be applied effiently with swift result.2 The thermal analysis is one of the most frequently used instrumental technique on pharmaceutical research solve technological problem3-6.thermoanalytical technique can be applied successfully to investigated different material from solid, semisolid, liquid, which have pharmaceutical relevance7-10. Thermo analytical technique are widely applied alone or as combined with microscopy, spectroscopy (UV, IR X- ray powder diffractometry and mass spectrometry11-13.However no universally protocol is available for evaluating the compatibility of drug with different excipients. Some of the reported methods have poor predictive values and few of them are labor intensive and time consuming. For example, FT-IR, Differential scanning calorimetry (has been proposed as a rapid method for evaluating the drug-excipient intraction14-19. Though it has certain advantages, such as requirement of small sample size and fast results, there are certain limitations also. This is because of exposure of drug-excipient mixture to high temperatures (up to 3000C or more which in real situation, is not experienced by the dosage form. Therefore the DSC results should be interpreted carefully, as the conclusions based on the DSC results alone can be often misleading and inconclusive20-22.

 

 

Fig.no.1 Gatifloxacin+ Methyl Paraben

 

Fig.no.2-Gatifloxacin+ Acacia

 

Fig.no.3-Gatifloxacin+ polyvinyl alcohol

 

Fig.no.4-Gatifloxacin + Hydroxyl propyl methyl cellulose

 

Fig.no.5-Gatifloxacin

 

Differential scanning calorimetry (DSC  has been a standard method for the characterization of solid drugs for many years in particular for preformulatiion studies23-26. the technique is used in preformulation studies between drug and excipients often results in shift, appearance of endothermic or exothermic peaks and on the change of other enthalpic values on thermal curves obtained with DSC method.27 In suspected cases of incompatibility , IR spectrum of pure drug was compared with that of drug-excipient mixture and pure excipient.28

 

In the present study. For the development of liquid dosage form of Gatifloxacin IR and DSC were used to selected excipients. Mainly indicated for the treatment of geatritic and peadtric patients. In the first phase, IR and DSC were used to study the compatibility of Gatifloxacin with selected excipients. Those Excipients that were defined prototype formula were tested using IR. Finally, the developed formulations were evaluated after 3 months of storage at accelerated stability condition (400C and 75%RH).29

 

EXPERIMENTAL:

Material:

Gatifloxacin was gift sample from Dr. Reddy pvt. Limited Hyderabad India. Following chemicals and excipients were purchased from commercial sources and used such as Polyvinyl Alcohol (Sd fine Chem. Ltd. Mumbai), MethylParaben (Loba Chemie, Pvt. Ltd. Mumbai), HydroxyPropylMethylCellulose (Loba Chemie, Pvt. Ltd. Mumbai), Acacia (Loba Chemie, Pvt. Ltd. Mumbai).

 

Method:

DSC A differential scanning calorimetry Dell Japan in Nagpur university- was used for the thermal analysis of mixtures of drug and excipients. Excipients that were expected to be used in the development of formulation (emulsifiers, stabilizers, polymer and the maximum expected ratio were selected excipients (all passed through 60-mesh sieve were weighed directly in the pierced DSC aluminium panTable1 and scanned in the temperature range of 25-3000C under an atmosphere of dry nitrogen. Heating rate of 100C min was used and thermo grams obtained were observed for any interactions.

 

IR Spectroscopy:

IR spectra of drug and drug-excipient blend were recorded on an IR Spectrophotometer (Impact- in the range of 4000-500cm-1 using potassium bromide discs).

Table No.1-Change of Gatifloxacin melting peak in different mixture

 

S .no

Mixture

Melting peak of Gatifloxacin (°C)

Endothermal Temperature range (°C)

1

Gatifloxacin

165.76

200.15

2

Gatifloxacin+ HPMC

192.20

205.20

3

Gatifloxacin+PVA

192.20

205.20

4

Gatifloxacin+ Acacia

86.70

170.68

 

 

 

 

 

 

 

Preparation of sample:

For each excipient, stocks were prepared by dispensing 100:100(1:1 mg of excipients mix well and prepared binary mixture by volume into vials.

 

Storage and analysis of sample:

Binary mixtures of drug and excipient and control samples were stored at 40 or 50 room temperature and 500Cand 75%RH. After storage for 1-4 weeks the drug was analysis of FTIR Spectrometer and Differential scanning calorimetry analysis.

 

RESULT AND DISCUSSION:

FTIR Spectrometer:

Drug and excipient were taken for analysis. The FTIR spectrum of optimized drug-excipient was recorded using FTIR Spectrophotometer (Shimazdu 8400S using KBr pellet technique and analyze for characteristic absorption of various functional groups  

 

C=O stretching 1320,-OH 3550, -CH3 3100-3200, CO-Aryl alkyl ether strong bond 1250,-C=O stretching 1650. And drug with Hydroxyl propyl methyl cellulose, polyvinylpyrrolidone, poly vinyl alcohol and Acacia same absorption peak so compatible with each excipients in fig no.6, 7, 8, 9, and 10.

 

Fig.no.6- FTIR of Gatifloxacin

 

Fig.no.7- FTIR of Gatifloxacin+ HPMC

 

Fig.no.8- FTIR of Gatifloxacin+PVP

 

Fig.no.9- FTIR of Gatifloxacin+PVA

 

Fig.no.10-FTIR of Gatifloxacin+Acacia

 

Differential Scanning Calorimetry:

Thermogram of Gatifloxacin, and Physical Mixture of Gatifloxacin and Optimized binary mixture were recorded in a differential scanning calorimeter to characterize the solid state of the drug in the Gatifloxacin. The sample were placed in flat bottomed aluminium pans and heated over a temperature range of 30-300°C at a constant rate of 5°C/ min with purging of nitrogen (50ml/min), using alumina as a reference standard.

 

Drug-Excipient Compatibility Testing:

Selected DSC scan of drug and drug-excipient mixtures are shown in Fig.1-5. Thermal behavior of pure drug respective excipient and the combination of drug and excipient is compared in the DSC thermo grams. Peak transition temperature (Tpeak) and heat of fusion or enthalpy (ΔHf) of Gatifloxacin in various excipient mixtures table no.1

 

The DSC trace of Gatifloxacin showed a sharp endothermic peak at   . In majority of the cases, melting endotherm of drug was well preserved with slight changes in terms of broadening or shifting towards the lower temperature it has been reported that the quantity of material used. Especially in drug-excipient mixtures, affects the peak shape and enthalpy. Thus the minor changes in the melting endotherm of drug could be due to the mixing of drug and excipient, which lower the purity of each component in the mixture and may not necessarily indicate potential incompatibility.

 

CONCLUSION:

As a part of an ongoing project on the Compatibility study between Gatifloxacin and Pharmaceutical excipients, different excipients were tested for their compatibility with Gatifloxacin. This is true provided that the proper experimental parameters are selected and the quantative results are duly considered in the interaction of the results. In particular, performing the measurements under Gatifloxacin allowed finding quantitative indicators of interaction already from the analysis of the physical mixture not previously treated under stress conditions. Moreover, the analysis of the stressed systems has confirmed the predictive value of such indicators. The idea to study two different compositions (instead of the mostly studied 1:1 mass ratio) turned out to be particularly advantageous allowing evidencing the dependence of interactions on system composition. Present study has demonstrated the successful utilization of techniques of DSC and FTIR to assess the compatibility of Gatifloxacin with the excipients used in the development of suspension formulations.

 

Based on the result of DSC alone, majority of the excipients were found to be compatible with Gatifloxacin. However, result showed that there might be some interactions between all the excipients that were defined in the prototype formula were found to be compatible with Gatifloxacin. Using the results of this study, suspension of Gatifloxacin were developed using the compatibles excipients. The optimized formulation was peaked in amber color glass bottle 1month of stability studies. In conclusion, DSC and FTIR were successfully used to select the excipients for suspension formulations of Gatifloxacin and the developed formulations were found to be stable after stability studies.

 

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Received on 09.01.2010

Accepted on 20.02.2010   

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Research Journal of Pharmaceutical Dosage Forms and Technology. 2(1): Jan. –Feb. 2010, 103-106