Stability of Piroxicam As Its And With Selected Pharmaceutical Excipients

Transcription

1 Research Article ISS: Anwar A.Wassel / Journal of Pharmacy Research 2011,4(10), Available online through Stability of Piroxicam As Its And With Selected Pharmaceutical Excipients Anwar A.Wassel ational organization for Drug Control and Research,P.. 29 Cairo,Egypt. Received on: ; Revised on: ; Accepted on: ABSTRACT The thermal analysis (DTA,TGA) and mass specttrometry (Ms) have been used to study the stability of piroxicam in dry air flux.the kinetic energy was KJ/mol and freqency factor 1.49 x mim-1.reformulation evaluation, using thermal analysis techniques (TGA, DTG and DTA) have come to the forefront as a valuable tool in achieving this goal. These articles evaluate the drug Piroxicam, alone and in combination with selected pharmaceutical excipients are typically used to prepare tablet, and capsule dosage form. To maximize tendency of an interaction, binary mixtures (1:1by weight) of drug and excipients, and between expectants were utilized. The change in reactivates, and the thermal behavior of materials under investigation was studied. The results show that no change in the properties of Piroxicam in presence of excipients, but its reactivity is affected. Key words: Piroxicam; Thermal analysis; Mass spectrometry Pharmaceutical Execipients ITRDUCTI: Piroxicam is a non-stradial anti-inflammatory drug, which displays potent anti-inflammatory and analgesic used in the symptomatic management of soft-tissue injury (1). and is effective in the treatment of rheumatoid. Piroxicam was name clotted according to IUPAC system as 4-hydroxy-2-methyl--(2- pyridyl)-2-1,2-benzothizine-3-carboxamide1,1-dioxide. Polymorphic and peudoplymorphic forms of drugs belonging to the oxicam class of non-steroidal anti-inflammatory drugs, whose x-ray structures have been reported, include the crystal forms of piroxicam [2,3]. The crystal and molecular structure of two polymorphs of piroxicam pivalate was studies [4]. TG-DTG finds increasing use in the pharmaceutical industry to study compatibility in tablet formulations and to assess whether it can be used analytically in mixture[5]. When a tablet containing one or more active drugs and excipients is produced, it becomes important to characterize possible interactions between the active drugs and /or excipients. If there are significant interactions, this could have an adverse effect on the bioavailability and shelf life time properties of the tablet. Thermal analysis can be used to characterize possible interactions between the active drugs and excipients for a particular tablet formulation [6-9]. This study uses thermal analysis to study(i) the decompostion mechanism and thermal stability of piroxcam as its, (ii) effect of these excipients, to determine the degradation pattern at elevated temperatures in an atmosphere of nitrogen. The copatibility of piroxicam with its binary mixtures of lactose, lauryl sulfate, and starch. EXPERIMETAL: MATERIAL: All chemicals employed in the present work were of analytical grade supplied by Pfizer Egypt Pharm.Company. Piroxicam, Lactose, Starch and Sodium louryl sulfate potency 99.9 % 1- Thermal analysis (TG, and DTA): The TGA and DTA studies were made with conventional thermal analyzer (Shimadzu DTA-50, Shimadzu TGA-50). 2- Mass spectral measurements and instruments The mass spectrum of pirxicam was recorded with EI technique at 70 ev on a ewlett-packard MS-5988GC instrument in the Micro-analytical Center, Cairo University. Procedure: 1-The experiments were performed between ambient and C.The temperature program had a heating rate 10 0 C /min from ambient to C.Dry nitrogen at a flow rate of 30ML/min was used as the purge gas. The flow rate *Corresponding author. Anwar A.Wassel ational organization for Drug Control and Research,P.. 29 Cairo,Egypt. was measured using an electron flow meter, (Jac-Scientific, Model # ADM 1000). The sample mass was kept, in the range of 5 mg. Platinum crucible of 110 ml capacity were used as the sample holder and reform. 2- A group of TG curves mouser at more than three heating rate is necessary (5,10,15 0 C /min). The TG curves shift to higher temperatures with increasing heating rate. A group of parallel curves will be obtained if the reaction is not changed. We used thermal analysis software program for the determination of activation energy, order of reaction. 3- In order to obtain obvious results of the interactions of these solid materials, the combinations of an equivalent ratio (W/W) binary mixtures were prepared instead of an actual ratio using a commercial formulation. The binary mixtures (1:1 by weight) were mixed in a poreclain morter. The experiments were carried out in an atmosphere of dry nitrogen at the flow rate of 30 m/ ml. RESULTS AD DISCUSSI: MS. Combination of the experimental techniques (MS and TG) is very important to understand the following topic. a-the stability of the drug as neutral molecule and ionized molecular ion. b-the primary sites of fragmentation mechanism. c-the selection of the most probable decomposition pathway of Piroxicam by both TA and MS.[10] A Typical TG, DTG, and DTA plots for Piroxicam in nitrogen are shown in Fig. (1). From the DTA plot, the melting of Piroxicam can be seen at C, followed by an endothermic peak at C, due to decomposition of Piroxicam. A hump due to polymorphism of Piroxicam can be observed at 57 0 C [4]. The thermo-analytical calculations have been done one the Piroxicam drug using zawa method Fig.(a) and the thermal decomposition parameters including activation energy E* (K J mol -1 ), rate constant (m -1 ) and the percentage of the weight loss are represented in table (1) Table (1) kinetic parameters determined from TG of Piroxicam Weight loss(%) Kinetic energy K J mol Average CV 4.279% These thermo-analytical data reveal that Piroxicam is successfully decomposed through five (5) stages with very frequency factor values (1.49 x mim-1) and half life time ranged ( x10-10 s.the TGA curve of Piroxicam refers to two stages of mass losses at temperature ranges and C 0. These stages involved mass losses of 92.8% and 4.4% for the first and second step decomposition, respectively.

2 Anwar A.Wassel / Journal of Pharmacy Research 2011,4(10), Mass spectral behavior of Piroxicam (MS) Electron ionization (EI) mass spectra of Piroxicam drug at 70 ev where recorded and investigated. A typical mass spectrum of the drug is show in Fig. (b). The main fragmentation path following electron impact Piroxicam my be rationalized to elimination of the molecular ion [M] as represented by scheme- 1. The mass spectrum of Piroxicam shows a well-defined parent peak at m/z =331 (M ) with a relative intensity = 21.7%. The C 3 3 ion, m/z = 172, RI (relative intensity) = 100% is the base beak in the spectrum of Piroxicam. The parent ion and other fragmentation are obtained by cleavage in different positions in the Piroxicam molecule and, the possible fragment ions are shown in scheme-1 m/z = 175 (F R.I = 100%) -156 S m/z = 331 (F R.I = 21.7%) m/z = 267(F.R.I=20%) m/z = 78 (F. 78. R.I = 34%) m/z = 162 (F R.I = 37%) -41 m/z = 92 (F. 94. R.I = 25%) Scheme 1: Mass fragmentation pattern of Piroxicam m/z =121 (F R.I = 32%) A Typical TG, DTG, and DTA plots for the starch in nitrogen are shown in Fig. (2) This shows the loss of water up to around 70 0 C, the degradation of the starch to carbon over the range C, followed by a slow loss of weight from the carbon residue beyond this temperature up to C where the experiment was stopped. Fig.(a) Kinetic thermal analysis calculation ( by zawa method) of Piroxicam. Mixtures of piroxicam and starch were examined using the thermal analysis unit. Fig. (3) Shows typically TG, DTG, and DTA plots for a (1:1) mixture in nitrogen. It can be seen that all the characteristics of the piroxicam can be discerned, namely, the melting (shown on DTA plot ) followed by the decomposition process. The loss of moisture from the starch can be seen on the TG plot, and the separate degradation of the starch can be observed. All the processes were endothermic. A Typical TG, DTG, and DTA plots for lactose in nitrogen are shown in Fig. (4) Both the TG / DTG and DTA plots demonstrate that lactose decomposes by three steps and percent weight loss of lactose is approximately 5% at the first stage, 11.5% at the second stage and 68% at the third stage on the TG curves. The peak temperature of the first peak is C from DTG curve the second peak has the peak temperature of C, and the partial tail of this peak overlaps with the third decomposition peak. The third peak temperature is C from the DTG curve reading. owever, four peak temperatures can be obtained from the DTA curve readings as 152,211.9, and 322,0 0 C.

3 Anwar A.Wassel / Journal of Pharmacy Research 2011,4(10), Fig.(b) Mass spectra fragmentation of Piroxicam

4 Anwar A.Wassel / Journal of Pharmacy Research 2011,4(10), Fig.10. The plots for all the binary mixtures of piroxicam with the excipients under investigation do not show any additional endothermic or exothermic peaks. ence, this suggests that these excipients are suitable to use in piroxicam solid-state formulations. The influence of pharmaceutical excipients on the thermal decomposition of piroxicam was obtained using the (Wtheoretical versus W experimental) method. Theoretical TG plots of the binary mixture of this material with the excipients were generated and compared with those obtained experimentally. owever, this method only provides the reactivity information for substances being compared in terms of more and less reactive than its theoritical values. This method would be reliable when the experimental conditions are identical Figs. (8,9,10). TG curve for the mixture of Piroxicam with starch is shown in Fig.(8) together with a theoretical curve which constructed by combining the TG signal of the individual substances of the mixture and then divided by tow. This theoretical curve is based on no-interaction between the tow components. The TG signal for the binary mixture of Piroxicam with sodium lauryl sulphate is shown in Fig. (9). The theoretical curve, constructed on the same basis of no-interaction of the two components shows some shift for the experimental curve for sodium lauryl sulphate to a lower temperature but the curves for the degradation of lauryl sulphate coincide. Fig.8. owever the TG plot for the binary mixture of Piroxicam and lactose shows large differences between the experimental curve and that calculated for 50:50 % binary mixture based on no-interaction between the components as shown in Fig.(10). This is not just due to the fact that the temperatures of decomposition for the two components coincide but must be due to some interaction between the component and/or their reaction products. Fig.9. Fig.(5) show a typical TG,DTG and DTA plot for 50:50% by mass of piroxicam and lactose,it can be seen that all characteristics of piroxicam as it is and there is no any shaft in the melting point of piroxicam by mixing with lactose.it is observed that on mixing Piroxicam and lactose a yellowish mixture is preduced indicating that a physical change occur Also, the mixture of (1:1) piroxicam with sodium lurayl sulfate was examined using TG, DTG, and DTA as show in Fig.(6,7) As been evident, no change on the characteristics of both piroxicam and sodium lurayl sulfate specially melting point of piroxicam. The difference in the experimental % mass loss between the theoretical and the experimental TG curve cane be attributed to the difficulty of making up perfectly 50% mixture [11] n comparison of the superimposed theoretical and experimental TG plots, deceleration of the decomposition of the mixtures was found in the presence of starch, sodium lurayl sulfate, and lactose. Conclusions: This study provides further insights into applicability of experimental TA and MS techniques on Piroxicam drug. From the applications of both techniques in commitment it is concluded that. The primary fragmentation of Piroxicam by applying both experimental techniques (TA and MS) can be explained by S2 gas loss from initial Piroxicam. Analysis of the thermal data indicates that the binary mixtures of Piroxicam with selected excipients, lactose, sodium lurayl sulfate, and starch, do not show any additional endothermic or exothermic peaks. This suggests that these excipients are suitable to use in solid state of Piroxicam formulations. REFERECES: 1. J.G.Lombardino, E..wiseman, Trends Phamacol.Sci., 2(1982) G.Reck, G.Dietz, G.Laban, G.Guenther,W.,G. Binnier, E. oethne., Pharmaze,43(1988) B.Kojic-Prodic,Z. Ruzic-Toros., Acta Crystalogr.,B38 (1982)

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