Department of pharmaceutical chemistry
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ItemDevelopment of Derivative and Difference Spectrophotometric methods for the analysis and stability studies of some veterinary antibiotics(University of Khartoum, 2017)Abstract Background Colistin, Florfenicol and Lincomicin chemical structures incorporate functional groups liable to chemical and photochemical reaction. Therefore, stability studies were conducted on these drugs to perform their chemical and photostability evaluation. In addition, Derivative spectrophotometric and Difference spectrophotometric methods were developed for the quantitative analysis of those drugs. The objectives of this study were to develop simple, sensitive, accurate and validated Derivative spectrophotometric and Difference spectrophotometric methods for the determination of the selected drugs in their bulk and dosage forms, to study the degradation behavior of these drugs at different pHs and temperatures and the photochemical stability of the drugs using the developed stability-indicating methods. Methodology: The Derivative spectrophotometric methods for determination of the drugs were based on the measuring of the zero-order, first and second derivative spectra for Colistin at 280 nm,298 nm and 318 nm respectively, for Florfenicol at 267nm 274 nm and 281 nm respectively and for lincomycin at 194 nm 206 nm and 212 nm respectively. In the Difference spectrophotometric methods the purity percentage of the drugs was measured using zero order derivative spectra, while ∆D1 was applied by measuring the absorbance of the alkaline solutions of the drugs against their corresponding aqueous solutions. The decomposition of the drugs was monitored by the first and second derivative spectroscopy over the pH range 2.2-11. The effect of different sodium hydroxide concentrations coupled with different heating time intervals on drugs solutions degradation rate was also studied using the developed derivative spectrophotometric methods. The influence of different temperatures on the hydrolysis rate of the drugs was studied by the developed method using phosphate buffer of pH 9and pH 10. Drugs solutions were irradiated with sunlight to study their photostability
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ItemDevelopment of Stability – Indicating HPLC Method for the Determination of Levamisole Hydrochloride in Bulk, Oral Solution and Injection Dosage Form(University of Khartoum, 2018)Abstract Background: Levamisole hydrochloride injection and oral solution used as anthelmintic formulations in veterinary clinics in Sudan and other developing countries. Chromatography and specially HPLC, has become the method of choice for drug analysis . The study objective was to design, develop and validate stability indicating HPLC method for the analysis of levamisole hydrochloride in injection and oral solution dosage forms. Methods: Levamisole hydrochloride was dissolved in an appropriate diluent and chromatographic conditions were then optimized using different HPLC parameters (column, solvent, mobile phase, UV detection and flow rate) were studied to give efficient separation to separate drug from their dosage forms and to decrease the retention time of the peak for time saving. Linearity, accuracy, LOD, LOQ, robustness, range and precision were assessed to validate the developed method. Effect of acid, base, oxidation and heat on levamisole HCL as raw was studied using the developed method. Results: The best separation for aqueous solution of levamisole hydrochloride (20 µl) was achieved on C 8 (250cm*4.6, 5µm). Phosphate buffer (pH 8.0): acetonitrile (70:30%v/v) (eluent A) and Phosphate buffer (pH 8.0): methanol (50:50%v/v)) eluent B) were used as mobile phases at flow rate of 1.5 ml/min. UV detection at 215 nm resulted in the highest peaks’ intensity. The developed method was found to be linear with a correlation coefficient of 1.000, Beer’s law was obeyed in the concentration range of (10– 51) μg/ml and with LOD of (0.29, 0.22) and LOQ of.(0.89,0.67) in eluent A and eluent B respectively. Specificity was assessed based on the high percent recovery found in accuracy (minimum 98.4% and maximum 103.9%), The method was also proved to be precise with RSD% less than 2% in the two mobile phases. Stability studies showed that the drug solution was unstable under heat, acidic, oxidation and alkaline conditions. But show major degradation in the basic condition (41%) and minor degradation in acidic condition (5%). Conclusion: A selective, accurate and precise stability indicating HPLC method for analysis of levamisole hydrochloride in bulk and in their injection and oral solution formulations has been developed and validated in accordance with ICH guidelines. The developed method was found to be suitable for the routine analysis as well as for stability studies of this drug. مستخلص ألأطروحة الخلفية: يتم استخدام المستحضر الصيدلاني الذي يحوي ليفاميزول هايدروكلوريدفي شكليه الصيدلاني حقن وشراب فموي على نطاق واسع في العيادات البيطريه في السودان والدول الناميه. طرق الفصل الكروماتوغرافي وخاصة نظام الكروماتوغرافيا السائله عاليه الاداء أصبحت الطريقة الامثل في تحليل الدواء. الهدف من الدراسة هو إستحداث وتصميم وتطوير ودراسه الفعاليه لطريقه تحليل ودالة على الثبات لعقار ليفاميزول هايدروكلوريد في شكله الخام والصيدلاني بإستخدام الكروماتوغرافيا السائله عاليه الاداء. الطرق: تمت إذابة عقارليفاميزول هايدروكلوريد في المذيب المناسب ومن ثم دراسة العوامل المتغيره المختلفة في نظام الكروماتوغرافيا السائله عاليه الاداء (العمود،المذيبات،الطورالمتحرك،والطول الموجي،ومعدل التدفق ) لإعطاءفصل فعال لفصل العقار من اشكاله الصيدلانية وتقليل الزمن اللازم لفصله .وتم التحقق من الفعالية بالمقومات الآتيه (الخطية، الدقة ، الحد الأدنى للتحليل الكيفي، الحد الأدنى للتحليل الكمي,المتانة والمدى،). تمت دراسة تاثير كل من الاحماض والقلويات والاكسدة والتسخين على ثبات عقارليفاميزول هايدروكلوريد في شكله الخام باستخدام الطريقة المطورة. النتائج:تم الحصول على افضل فصل للطريقة المستحدثة على حقن (20 ميكروليتر) من المحلول المائي لعقارليفاميزول هايدروكلوريد باستخدام الطور الثابت سي 8 (250*4.6-5 ميكروليتر) وباستخدام الطور المتحرك)أ( المكون من محلول الفوسفات ثابت الرقم الهيدروجيني (الرقم الهيدروجيني 8.0) مع الاسيتونايترل بنسبة (70:30), و أيضا باستخدام الطور المتحرك ب المكون من محلول الفوسفات ثابت الرقم الهيدروجيني (الرقم الهيدروجيني 8.0) مع الميثانول بنسبة (50:50) بمعدل التدفق من5.1 مل / دقيقة. كما أدى استخدام الأشعة فوق البنفسجية 215نانومتر في جهاز الكشف الحصول على استجابة عالية. الطريقة المستحدثة لتحليل عقار ليفاميزول هايدروكلوريد في المدي من (10-51 ميكروجم/مل).وأنها خطية (معامل انحدار 1.000). كما وجد ان ألطريقة دقيقة (معدل الانحراف المعياري اقل من 2%). كما وجد أن الحد الأدنى للتحليل الكيفي لعقارليفاميزول هايدروكلوريدهو(0.29,0.22) ميكروجم/مل والحد الادنى للتحليل الكمي(0.89,0.67)ميكروجم/مل على التوالي للطورين المتحركين أ وب .اعتمدت إنتقائية الطريقة المستحدثة لعقارليفاميزول هايدروكلوريد علي نتائج اختبار الدقة التي تتراوح بين.(98.4% - 103.9%) عكست دراسة الثبات بإستخدام الطريقه المستحدثة ان عقار ليفاميزول هايدروكلوريد يكون اكثر ثبات عند تعرضه للحرارة وألاكسدة.ووجد انه يكون اكثر ثباتا في الوسط الحمضي (نقصان بنسبة5%) وأقل ثباتا في الوسط القلوي ( نقصان بنسبة 41%). الخلاصة:تم تطوير طريقه تحليل عقارليفاميزول هايدروكلوريد في شكله الخام وعلي هيئة حقن وشراب فموي ذات قدرة عالية من الدقة والاجادة والاستقامة دالة على الثبات بإستخدام نظام الكروماتوغرافيا السائلة عالية الدقة واثبتت الطريقة فعاليتها وفقا للمبادئ التوجيهية للمؤتمر الدولي المعني بالتنسيق, يوصى بإستخدام هذه الطريقة للتحليل الروتيني للعقار في شكله الخام والصيدلاني.
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ItemDevelopment of Derivative and Difference Spectrophotometric Methods for the Analysis and Stability Studies of Some Veterinary Antibiotics(University of Khartoum, )Background Colistin, Florfenicol and Lincomicin chemical structures incorporate functional groups liable to chemical and photochemical reaction. Therefore, stability studies were conducted on these drugs to perform their chemical and photostability evaluation. In addition, Derivative spectrophotometric and Difference spectrophotometric methods were developed for the quantitative analysis of those drugs. The objectives of this study were to develop simple, sensitive, accurate and validated Derivative spectrophotometric and Difference spectrophotometric methods for the determination of the selected drugs in their bulk and dosage forms, to study the degradation behavior of these drugs at different pHs and temperatures and the photochemical stability of the drugs using the developed stability-indicating methods. Methodology: The Derivative spectrophotometric methods for determination of the drugs were based on the measuring of the zero-order, first and second derivative spectra for Colistin at 280 nm,298 nm and 318 nm respectively, for Florfenicol at 267nm 274 nm and 281 nm respectively and for lincomycin at 194 nm 206 nm and 212 nm respectively. In the Difference spectrophotometric methods the purity percentage of the drugs was measured using zero order derivative spectra, while ∆D1 was applied by measuring the absorbance of the alkaline solutions of the drugs against their corresponding aqueous solutions. The decomposition of the drugs was monitored by the first and second derivative spectroscopy over the pH range 2.2-11. The effect of different sodium hydroxide concentrations coupled with different heating time intervals on drugs solutions degradation rate was also studied using the developed derivative spectrophotometric methods. The influence of different temperatures on the hydrolysis rate of the drugs was studied by the developed method using phosphate buffer of pH 9and pH 10. Drugs solutions were irradiated with sunlight to study their photostability. Results: Regression analysis of Beer's plot of the results obtained for analysis of the drugs showed good correlation not less than (r=0.998) in a concentration range of 800-4000 IU/ml, 3-15μg/ml and 3-15μg/ml for Colistin, Florfenicol and Lincomycin respectively. The assay and added recovery results were 98.8 ± 1.8 (n=3) & 99.7 ± 1.6 for Colistin, 100.70 ± 1.84 (n=3) & 98.3 ± 1.8 for Florfenicol and 101.10 ± 0.971 (n=3) &100.3 ± 1.3 for Lincomycin . The results obtained by the developed methods were statistically validated according to VICH guidelines, and evaluated at 95% confidence limits. The degradation of the drugs was found to follow first order reaction rate which was alkaline, pH and temperature dependent. The photochemical experiments conducted on drugs revealed their photostability the conditions used. The Difference spectrophotometric methods developed for drugs revealed excellent correlation coefficient (not less than 0.999) for the linearity ranges studied for them. The obtained results for the average recovery reflected no interference by the excipients found in the dosage forms. The obtained quantitative results for drugs were evaluated at 95% confidence limits. Conclusion: The developed Derivative and Difference spectrophotometric methods were proved to be simple, sensitive, accurate and precise for determination of the selected drugs Drugs were found to undergo hydrolysis in alkaline media which is pH and temperature dependant. The photochemical experiments showed the photostability of the drugs.
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ItemDevelopment of Stability – Indicating HPLC Method for the Determination of Methyldopa, Levodopa & Carbidopa in Bulk and Tablets Dosage Form(University of Khartoum, )Background Methyldopa, Levodopa and Carbidopa are three drugs with similar chemical structures and different pharmacological actions. This similarity made it difficult to distinguish between them in pharmaceutical analysis. Thus, development of selective methods for their routine analysis is highly needed. The current work aimed to develop and validate a selective HPLC method for the analysis of methyldopa, levodopa and carbidopa in bulk and pharmaceutical formulations. Methods Methyldopa, levodopa and carbidopa were dissolved in an appropriate diluent and chromatographic conditions were then optimized to separate the three drugs from their mixture. Linearity, accuracy, and precision were assessed to validate the developed method. The validated method was then applied for the analysis of the three drugs in bulk and pharmaceutical formulations and to study their stability under stress conditions. Furthermore the method was statistically compared with the official USP methods. Results Good resolution was achieved using the developed method. Constructed calibration curves were linear in the concentration ranges (25-250 μg/ml) and (2.5-25 μg/ml) for methyldopa, levodopa and carbidopa respectively with correlation coefficient not less than 0.999. The limit of detection (LOD) and limit of quantitation (LOQ) were (0.91 and 2.77) μg/ml for methyldopa, (3.77 and 11.44) μg/ml for levodopa and (0.98 and 2.96) μg/ml for carbidopa respectively. RSD% values were less than 2% which indicate the precision of the developed method. Comparison of the developed method with the official USP methods in terms of precision (using F test) and accuracy (using t test) showed that the developed method is precise (calculated F- value < tabulated one) for methyldopa and accurate (calculated t- value < tabulated one) for methyldopa and levodopa, while there was a significant difference (calculated F- value > tabulated one) in precision for levodopa and carbidopa and in accuracy (calculated t- value > tabulated one) for carbidopa. Stability studies showed that the three drugs solutions are unstable under heat and alkaline conditions. Methyldopa and carbidopa solutions were unstable under UV irradiation (254 nm), while levodopa and carbidopa solutions were unstable under UV irradiation (365 nm). Conclusion A selective, accurate and precise stability indicating HPLC method for analysis of methyldopa, levodopa and carbidopa in bulk and in their single or combined tablet formulations has been developed and validated in accordance with ICH guidelines. The developed method was found suitable for the routine analysis as well as for stability studies of these drugs.
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ItemDifferential Spectrophotometric Method for Determination of Drugs Possessing Phenol Functionality(University of Khartoum, )Background: The superiority of difference spectrophotometry when coupled with first derivative technique enhances the selectivity and cancels the interference of the excipients and other matrices as such this approach can be exploited to develop spectrophotometric stability indicting assay method. The aim of this work was to develop spectrophotometric stability indicating methods for the determination of drugs possessing phenol functionality in bulk and in pharmaceutical dosage forms. Amoxicillin (AMT) and paracetamol (PAR) were taken as models in this study. Methodology: The difference spectrum between equimolar solutions of the drug in 0.1 M NaOH and 0.1 M HCl was obtained by placing the drug solution in 0.1 M NaOH in sample cell and its solution in 0.1 M HCl in the blank cell. The first derivative spectrum of the produced difference spectrum was then recorded and the required data was extracted and analysed. To validate the proposed method; the linearity, recovery, limit of detection and limit of quantification were all determined using the data extracted from the spectra. Results: Beer’s law was obeyed in the concentration range of 5-25 µg/ml for amoxicillin with correlation coefficients (r=0.9998) and (r= 0.9996) at 249 nm and 292 nm respectively for zero order curve, the correlation coefficient for the first order curve at 257 nm was (r= 0.9998). The intercepts (a) were (0.00851 ± 0.019) and (0.0037 ± 0.0068) at 249 nm and 292 nm respectively, for zero order curve, and (0.0007 ± 0.00286) for first order curve. The slopes (b) were (0.024 ± 0.0012) at 249 nm and (0.0061 ± 0.00041) at 292 nm for zero order curve, and (0.0013 ± 0.00017) for first order curve. The methods recoveries were (99.2% ± 0.795) (103.04% ± 3.032) at 249 nm and 292 nm respectively using the zero order method, while it was (100% ± 0.00) using first order method. The limits of detections were (0.0348µg/ml) and (0.743µg/ml) at 249 nm and 292 nm respectively using zero order method, while it was (1.465 µg/ml) for first order method. The limits of quantification were (0.116 µg/ml) and (2.477 µg/ml) for zero order method at 249 nm and 292 nm respectively, and (4.885 µg/ml) for the first order method.On the other hand, Beer’s law was obeyed in the concentration range of 4-20 µg/ml for paracetamol, with correlation coefficients (r =0.9999) and (r = 0.9995) for the zero order and first order curves respectively. The intercepts (a) were (0.00192 ± 0.010) and (0.0005 ± 0.0024) for the zero order and first order curves respectively. The slopes (b) were (0.0436 ± 0.0008) and (0.0013 ± 0.0002) for the zero order and first order curves respectively. The minimum detectable concentrations were found to be 0.155µg/ml and (1.228µg/ml) for the zero order and first order method respectively. The lower quantification limit were (0.515µg/ml) and (4.095µg/ml) for the zero order and first order methods respectively. The methods recoveries were (99.42% ± 0.58) and (100% ± 0.00) for the zero order method and first order method respectively. Conclusion: The proposed methods were simple, fast, and accurate and they have stability indicating property. They can be applied for quality control and routine analysis of amoxicillin and paracetamol in bulk and in pharmaceutical dosage forms.