AComparativeStudyofMassAttenuationCoefficients forPharmaceuticalCompounds

Proceedings NSRP‐19, Dec. 12‐14, 2012 Mamallapuram, Tamil Nadu, India 35 A Comparative Study of Mass Attenuation Coefficients for Pharmaceutical Compounds Manjunath A, Rajeshwari T and B R Kerur* Department of Physics, Gulbarga University, Gulbarga – 585 106 (India) *kerurbrk@hotmail.com ABSTRACT A non-destructive analytical method was used to analyze the quality assurance of the pharmaceutical drugs by determining the mass absorption coefficient. The opted pharmaceutical product was a diclofenac sodium of different manufacturers such as Diclomol, Diclogesic, Dynapar and Voveran Plus at different energies from 13 keV to 33 keV using Am-241 primary source with Rb, Mo, Ag and Ba are the secondary targets of radioactive sources. The photon intensity is analyzed using a good geometry HPGe detector system coupled to PC based Multichannel Analyzer (MCA). The qualities of the above said samples are discussed by the obtained values of mass attenuation coefficient. Keywords: Attenuation coefficient, X-ray Spectrometric, Diclofenac sodium Introduction Analysis is a critical and integral part of the pharma business. Its only upon clearance of products on the analysis can the products be even released into the market. Hence, analytical methods as well as the involved analytical tools assume prime importance. Several well known analytical tools viz., HPLC, GC, IR, UV-Vis, atomic absorption spectrophotometer etc., are available to a pharmaceutical analyst. This article attempts to depict merits of the mass absorption spectrometer in estimation of quality assurance of the pharmaceutical products. Hence, in this approach Diclofenac Sodium tablets were chosen as the model drug for the study. The drug chosen for the study has a great importance due to its large clinical applications especially for the cases of arthritis, including both osteoarthritis and rheumatoid arthritis. Many researchers have carried out studies in determining the composition and concentration levels of diclofenac sodium in various commercially available tablets [1, 2]. A great number of experimental investigations have been performed to determine the mass attenuation coefficient for various materials such as elements, compounds, tissue equivalent compounds, mixtures, alloys, building materials, etc [3-9] at different photon energies. However, in the literature, there are almost no reports on the study of mass attenuation coefficient measurements for present pharmaceutical samples in the energy range 13 - 33 keV. In the present work, the mass attenuation coefficient of some pharmaceutical samples are determined at 13 keV to 33 keV using 241Am source and Rb, Mo, Ag and Ba secondary exciter are used to get photons in the above energy range. Sample Description The diclofenac sodium tablets are combination of paracetamol and diclofenac sodium in the proportion of 500 mg and 50 mg respectively. Paracetamol (p-hydroxy acetanilide) is a compound with analgesic and antipyretic properties. It is much safer than aspirin in terms of gastric irritation, ulceration and bleeding [10, 11]. Diclofenac sodium [2-[(2, 6-dichlorophenyl)] amino] benzene acetic acid monosodium salt] is a compound with potent anti-inflammatory property and belongs to a class of drugs called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). It affords quick relief of pain and wound edema [12, 13]. These are commonly used for the reduction of mild to moderate pain, inflammation, fever and stiffness as well as for medical conditions related to pain and inflammation. They work by inhibiting the action of certain hormones that cause inflammation and pain in the body. Diclofenac in combination with Paracetamol helps reduce headaches, body pain, menstrual and dental pain, sports and accident injuries, rheumatism, arthritis, lumbago, bursitis and sciatica. A few common side effects include sickness, an unexplained rash, and stomach pain. Hypothesis Of Attenuation Coefficient Low-Z materials are often used or considered for use as scattered of x-ray beams. These uses may originate from a desire to reduce the intensity of the x-ray beam, e.g., for diagnostic purposes, or may be required as a result of experimental geometry constraints. When radiations are allowed to pass through any materials its intensity is progressively decreases as a result of complex series of interaction between radiation and the atoms in the attenuating media. It is caused by both the absorption and scattering of the primary photons. A narrow beam of monoenergetic photons with incident intensity I0, penetrating an absorbing material with mass thickness x and density ρ, emerges with an intensity I is given by the exponential law as: (1) ⎞ ⎤ I = exp ⎡⎢ − ⎛⎜ μ I0 ρ ⎟⎠ x ⎥⎦ ⎣ ⎝ This equation can be rewritten as: μ −1 ⎛ I ⎞ ρ = x ln ⎜⎝ I 0 ⎟⎠ (2) from which μ/ρ can be obtained from measured values of I, I0 and x. Note that the mass thickness is defined as the mass per unit area and is obtained by multiplying the thickness t by the density ρ i.e., x = ρt If the absorber consists of a chemical compound or a homogeneous mixture, the mass attenuation coefficient can be calculated approximately from the weighted average (by mass) of the individual mass attenuation coefficients of the constituent elements in the compounds are usually estimated by using the Bragg’s additivity law commonly called as the mixture rule is given as; Proceedings NSRP‐19, Dec. 12‐14, 2012 Mamallapuram, Tamil Nadu, India μ ρ = ∑ i ⎛ μ ⎞ ⎟⎟ ⎝ ρ ⎠ ω i ⎜⎜ 36 (3) i where (μ/ρ)ι is the mass attenuation coefficient for the ith element and ωi, is its weight fraction of the ith element. The mass attenuation coefficient can also be expressed as barns per atom through the expression: (4) σ (barns / atom ) = ⎛⎜ A N ⎞⎟ x10 −24 ⎛⎜ μ ρ ⎞⎟(cm 2 / gm ) ⎠ ⎝ A⎠ ⎝ where A is the atomic weight of the absorber material and NA is the Avogadro's number. The attenuation coefficient, photon interaction and related quantities are functions of the photon energy. The total cross section can be written as the sum over contributions from the principle photon interactions. (5) σ = σ +σ +σ +σ +σ +σ pe coh incoh pair trip ph.n where σpe is the atomic photoelectric cross section, σcoh and σincoh are the coherent (Rayleigh) and incoherent (Compton) scattering cross sections, respectively σpair and σtrip are the cross sections for electron – positron pair production in the fields of the nucleus and of the atomic electrons, respectively and σ ph.n is the photonuclear cross section. Photonuclear cross section can contribute as much as 5% to 10% of the total photon interaction in the energy range of 5 MeV to 40 MeV. Experimental Procedure The preferred diclofenac sodium tablets from various firms (manufacturer) such as Diclomol, Dynapar, Diclogesic and Voveran plus, across the country (India) were collected from the medical dispensaries. The drug composes acetaminophen commonly called as paracetamol and diclofenac sodium in the proportion of 500 mg & 50 mg Fig.1 : respectively. The tablets were grind to a fine powder to pelletize the samples of variable thickness with an area of 1.327 cm2 using hydraulic pellet machine. The X-ray spectrometric technique comprising the High Purity Germanium (HPGe) detector was adopted to determine the mass attenuation coefficients [8]. Am-241 was used as primary source and Mo, Ag, Ba and Rb were used as target to produce the x-rays in the energy range 13 to 33 keV. The good-geometry experimental arrangement is shown in Fig. 1. X-rays emitted from the variable energy x-ray source, S passes through the collimator C1 and are incident on the absorber A (pellets) of different thickness kept normal to the photon beam. The transmitted beam passing through collimator C2 are detected by a high resolution HPGe x-ray detector system D. To measure the transmitted intensity (Beer-Lambert’s law) accurately it is important that the sample is mounted exactly normal to the x-ray beam. The transmitted x-ray spectrum can be recorded using a PC based multichannel analyzer and the mass attenuation coefficients can be measured using equation (1). The obtained mass attenuation coefficients of the samples were compared with the theoretical values using WinXcom software at above energies. For the compounds the theoretical mass attenuation coefficients are determined from the additivity law. The percentage deviations (PD) mentioned in Table 1 indicates the deviation of experimental values from the corresponding theoretical values and is given by (μ ρ )exp − (μ ρ )th (6) Percentage Deviation = x 100 (μ ρ )th Results And Discussion The experimental and theoretical results of mass attenuation coefficient of the diclofenac sodium tablets from different firms have been tabulated in table 1. Schematic diagram showing the experimental setup for the measurement of μ/ρ Proceedings NSRP‐19, Dec. 12‐14, 2012 Mamallapuram, Tamil Nadu, India 37 Table 1: Mass Attenuation Coefficient for the diclofenac tablets of different firms at different energies Name of the sample Mass attenuation coefficient in (cm2/g) Expt 5.0 PD (%) 4.5 4.0 WinXcom 3.5 2.36 -53.88 Diclomol 2.18 Dynapar 2.13 -58.37 Vovaran Plus 1.81 -64.63 -57.40 2 Diclogesic μ/ρ in cm /g 13.395 KeV 5.1168 Diclogesic Diclomol Dynapar VoveranPl WinXcom 5.5 3.0 2.5 2.0 1.5 1.0 0.5 17.481 KeV Diclogesic 1.60 0.0 -34.17 2.4307 Diclomol 1.41 Dynapar 1.13 -53.51 Vovaran Plus 0.92 -62.15 20 25 30 35 Energy in Kev Fig.2 : Variation of mass attenuation coefficient of diclofenac sodium tablets of different manufacturer. Conclusions Diclogesic 0.78 -39.65 Diclomol 0.46 Dynapar 1.03 -20.30 Vovaran Plus 0.32 -75.24 -64.41 32.2 KeV Diclogesic 0.20 Diclomol 0.17 -63.25 Dynapar 0.72 +32.30 Vovaran Plus 0.66 +21.28 0.5442 15 -41.99 22.16 KeV 1.2924 10 -68.76 It is clearly seen that the mass attenuation coefficient depends on the photon energy and on the chemical composition of the composite materials. The μ/ρ values decrease with increasing photon energies as shown in the fig 2. The total uncertainty of measured mass attenuation coefficient depends on the uncertainties in the evaluation of peak area, mass thickness measurement and counting statistics. The agreement between the experimental and theory is within the experimental uncertainty. Photoelectric cross section is the predominant process in the low energy region, coherent and Compton scattering are very small. The total cross section is considered as the function of energy, incoherent scattering process is predominant to a greater extent and coherent scattering remains the same for increasing energy. There is a linear alignment in the value of μ/ρ for Diclomol and Diclogesic with respect to the theoretical results, while the remaining two are not, this is because of the manufacturers hidden additive material added in their drug samples was not displayed on the packet. The errors involved in the experimental data are within 2% in each sample. Dynapar and Voveran plus were showing an increasing μ/ρ values rather the decreasing at 22.16 KeV and 32.2 KeV respectively. The developed X-ray spectrometric method was found to be simple, inexpensive, non destructive and helpful for precise accurate relative intensity measurements of the drug samples. 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