INTRODUCTION:

Drug-excipients compatibility can alter the physicochemical properties and bioavailability of the drugs. This incompatibility there by affects its safety and/or efficacy. Study of the drug excipients compatibility is an important process in the development of the stable solid dosage form and it helps in the selection of right excipients. This increases the probability of developing a stable dosage form. Despite of the importance of the drug-excipients compatibility tests, there is no universally accepted protocol for this purpose. The term thermal analysis refers to the group of techniques in which physical property of a substance is measured as a function of temperature. Differential scanning calorimetry (DSC) technique involves the application of a heating or cooling signal to a sample and a reference. When the substance undergoes a thermal event, the difference in heat flow to sample and reference is monitored against time and temperature. As a result, energy associated with various thermal events (e g melting, glass transition temperature and crystallization etc.) can be evaluated¹. This method can be extensively reported in the literature for the testing of the compatibility of the excipients with number of drugs.² Infrared spectroscopy is a technique based on the vibrations of the atoms of a molecule.

An infrared spectrum is commonly obtained by passing infrared radiation through a sample and determining what fraction of the incident radiation is absorbed at a particular energy. The energy at which any peak in an absorption spectrum appears corresponds to the frequency of a vibration of a part of a sample molecule. UV spectrophotometric method is common analytical techniques used to determine the drug content of most of the drugs. In the present study, the drug excipients compatibility of the gatifloxacin with various excipients was determined by isothermal stress testing (IST) as a part of an ongoing project on the development of extended release formulation of gatifloxacin. DSC, FTIR and UV spectrophotometric methods were used for the characterization study.³

EXPERIMENTAL:

Gatifloxacin was obtained as a gift sample from Dr. reddy laboratories Pvt. Ltd (Hydrabad, India).Acacia, Polyvinyl alcohal and Hydroxy propyl methyl cellulose (HPMC) was obtained from loba chemicals Mumbai, India. All other chemicals and reagents used in the study were of analytical grade.

The drug and polymer mixtures of gatifloxacin with various excipients prepared at 1:2 ratio. The drug and different polymers were individually weighed in a 10 mL glass vial and mixed on a vortex mixer for 2 min. In each of the vials, 10% of the water was added and the drug-excipient blend was further mixed. Each vial was sealed Teflon-lined screw cap and stored at 50°C for 4 weeks. These samples were periodically examined for any change of unusual color change.⁴

Characterization by UV spectrophotometer:

The samples after 4 weeks were withdrawn from storage and analyzed by UV spectrophotometric. The drug content was determined at initial and stored samples in triplicate. An accurately weighed amount of the drug-polymer mixture was taken and suitably dissolved under sonication (Power sonic 505, HWASHIN technology co) in pH 6.8 phosphate buffer and filtered through 0.45 μ (Millipore) filters. The sample was analyzed after making appropriate dilutions using UV spectrophotometer (Schimadzu, UV-1700 E 23) at 271 nm against blank.⁵

Fourier transforms infrared radiation measurement (FT-IR):

The FT-IR spectra acquired were taken from dried samples. A FT-IR (Thermo Nicolet 670 spectrometer) was used for the analysis in the frequency range between 4000 and 400 cm-¹, with 4 cm-¹ resolution. The results were the means of 6 determinations. A quantity equivalent to 2 g of pure drug and matrix tablets were selected separately.⁶

Differential scanning calorimetry (DSC) study

Differential scanning calorimetry (DSC) study of matrix tablets was performed using a Diamond DSC (Mettler Star SW 8.10) to determine the drug-excipients compatibility study. The analysis was performed at a rate 50⁰C min -¹ from 50 to 200⁰C temperature range under Nitrogen flow of 25 mL min -¹.⁷This clearly indicates the stable nature and no interaction of the gatifloxacin with excipients (Figure 1,2).

RESULTS AND DISCUSSION:

Drug content estimation

The drug and excipients mixture was physically observed at different intervals. No Characteristic color change was observed. The assay of the drug excipients mixtures were found good. Assay value of 99.12 to 100.1 was observed at initial. Good correlation was observed with the samples of drug excipients mixtures stored at 50°C for 4 weeks. This clearly indicates the stable nature of the gatifloxacin with excipients (Table 1).

Table 1. Drug content of Gatifloxacin at initial and storage at 50 °C for 4 weeks.

	Drug-Acacia	Drug-PVP	Drug-HPMC
Initial	99.33	99.56	99.12
50 °C for 4 weeks	99.11	99.02	99.32

Fourier transforms infrared radiation measurement (FT-IR).The characteristic band peaks acquired were taken from the prepared drug- excipients mixtures. The interaction study between drug and excipients was evaluated. The characteristics peak of the carbonyl group present in the cystedine nucleus at 1650 cm-¹, a band of peaks at 3325 and 3203 cm-¹ owing to amino and hydroxyl groups. Peaks at 1285 and 1160 cm-¹ owing to asymmetrical and symmetrical stretching of C-O-C system present in the oxathiolane ring conforms the stable nature of the drug in the excipients mixture (Figure 3). Differential scanning calorimetry (DSC) studies ^8-15 of drug- excipients mixtures were performed using a Diamond DSC (Mettler Star SW 8.10) to determine the drug excipients compatibility study. The analysis was performed at a rate 50^oC min-¹ from 500 to 2000^oC temperature range under nitrogen flow of 25 mL min-¹. Thermograms of pure gatifloxacin showed sharp endothermic peak at 180°C. Similar peaks were obtained in the prepared drug- excipients mixtures. This clearly indicated the nil drug polymer interaction.

Figure 1-DSC Gatifloxacin+PVA

Figure 2-Gatifloxacin+Acacia

Figure 3-IR of Gatifloxacin

SUMMARY AND CONCLUSIONS:

No characteristic color change was observed during the storage at 50°C for 2 weeks. Good correlation was observed at initial and during IST. This clearly indicates the stable nature of gatifloxacin with the excipients used in the present study. FTIR study of the initial and IST clearly indicates the stable nature of the gatifloxacin. DSC study conform the stable nature of the gatifloxacin during isothermal stress testing. This study is defiantly useful for the preparation of gatifloxacin extended release formulations.

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Received on 29.05.2011 Modified on 08.06.2011

Research J. Pharm. and Tech. 4(8): August 2011; Page 1216-1218