COMPARATIVE STUDY OF RP-HPLC METHOD VERSUS FOURIER TRANSFORM CONVOLUTION CHEMOMETRIC METHODS; AN APPLICATION ON PHARMACEUTICAL BINARY MIXTURES OF CANDESARTAN CILEXETIL-PITAVASTATIN CALCIUM AND CLOPIDOGREL BISULFATE-ROSUVASTATIN CALCIUM

Objective: A comparative study of smart spectrophotometric chemometric assisted techniques and RP-HPLC for the determination of candesartan cilexetil (CAN)-pitavastatin calcium (PIT) and clopidogrel bisulfate (CLO)-rosuvastatin calcium (ROS), binary co-administered drugs were developed and validated.Methods: The spectrophotometric chemometric assisted methods included two simple techniques, namely Fourier transform convolution (FF) and ratio spectra of Fourier transform convolution (FFR) methods. FFR is considered as a hybrid divisor ratio spectra method where Fourier functions are applied to divisor ratio signals. The RP-HPLC method involves a rapid separation on a C18 column using a mobile phase consisting of acetonitrile: sodium dihydrogen phosphate (adjusted to pH 2.6 using orthophosphoric acid) in the ratio of 70:30 v/v at a flow rate of 1 ml/min in isocratic mode. CLO and ROS were monitored at 220 nm however CAN and PIT were monitored at 238 nm.Results: The spectrophotometric chemometric assisted methods proved their ability to quantify each of the studied drugs in their binary mixtures, where excellent percentage recoveries were obtained. FF and FFR method proved to be linear over the concentration range of 10-50 µg/ml for CLO, 4-20 µg/ml for ROS, 8-20 µg/ml for CAN and 2-10 µg/ml for PIT. The RP-HPLC method was able to separate the drugs in the study; retention times were found to be 3.9 min and 14.4 min for ROS-CLO, 4.2 min and 14.5 min for PIT-CAN respectively. The RP-HPLC method was found to be linear in the concentration range of 0.1-0.5 µg/ml for CLO, 0.04-0.2 µg/ml for ROS, 0.5-1 µg/ml for CAN and 0.05-0.1 µg/ml for PIT. System suitability parameters proved that peaks were well resolved from each other.Conclusion: The spectrophotometric and chromatographic methods were validated according to ICH guidelines. Recovery was found to be in the range of 95.9 %-100.5 % in synthetic laboratory mixtures. The suggested spectrophotometric methods have the advantage over other methods that they do not require a preliminary separation. Statistical analysis between the suggested spectrophotometric chemometric assisted and RP-HPLC methods, using student's t-and F-test revealed that there is no difference between the applied methods

ANALYSIS OF THREE CARDIOVASCULAR DRUGS IN THEIR TERNARY MIXTURE USING GREEN ANALYTICAL METHODOLOGY OF SMART SPECTROPHOTOMETRIC METHODS AND RP-HPLC METHOD

Objective: Development and validation of two new, simple and specific analytical techniques for the simultaneous determination of a ternary mixture of co-administered cardiovascular drugs ticagrelor (TICA), irbesartan (IRB) and hydrochlorothiazide (HCT).Methods: Chemometric assisted UV spectrophotometric methods (considered as green analytical chemistry) and RP-HPLC method were developed and validated. The different applied chemometric methods are based on Fourier function convolution (FF) and Double divisor ratio spectra Fourier function (FFR). As for the HPLC method, it was developed on a C18 Sunfire© waters column with a mobile phase composed of Acetonitrile: sodium dihydrogen phosphate (adjusted to pH 3.6 using orthophosphoric acid) in the ratio of 60:40 v/v at a flow rate of 1 ml/min. Quantification was based on measuring peak areas at 230 nm.Results: By applying the chemometric assisted methods, good percentage recoveries were obtained in quantifying each of the drugs in their triple mixture. The RP-HPLC method, peaks were well resolved with retention times 4.6, 8.0 and 10.0 min, for HCT, TICA and IRB, respectively. The established method was also applied in samples spiked with plasma; the peaks were well separated from each other and from plasma protein peaks, proving the ability of the HPLC method to be applied in biological samples. The methods (RP-HPLC and chemometric assisted methods) were validated in terms of linearity, LOD, LOQ, precision and accuracy. The results obtained from the analysis of the co-administered mixture by the proposed chemometric assisted methods were statistically compared to those obtained by the applied RP-HPLC method.Conclusion: The applied RP-HPLC methods were proved to be more sensitive when compared to the applied chemometric methods, thus could be used for determination of drug concentration in human plasma. However, the applied chemometric methods, considered as green analytical chemistry, is a simple, time-saving method that requires minimal use of a hazardous solvent.Â

DEVELOPMENT AND VALIDATION OF ANALYTICAL SPECTROPHOTOMETRIC AND RP-HPLC METHODS FOR THE SIMULTANEOUS ESTIMATION OF HYDROQUINONE, HYDROCORTISONE AND TRETINOIN TERNARY MIXTURE IN TOPICAL FORMULATION

Objective: Development and validation of spectrophotometric and RP-HPLC methods for the simultaneous determination of Hydroquinone (HQ), Hydrocortisone (HC) and Tretinoin (TRT) ternary combination in pharmaceutical preparation. Methods: The proposed spectrophotometric method was able to determine TRT directly from its absorption spectrum at 362 nm, however, HQ and HC from their first derivative spectra at 284 nm and 252 nm, respectively, without any separation step. The RP-HPLC method was developed using a C18 Sunfire© waters column with a mobile phase composed of acetonitrile: phosphate buffer (adjusted to pH 6.1 using ortho-phosphoric acid) in the ratio of 30:70 %, v/v, respectively at a flow rate of 0.8 ml/min. Quantification was based on measuring peak areas at 260 nm. Results: The spectrophotometric method was able to selectively quantify each of HQ, HC and TRT in the ranges of 10-50 µg/ml, 2-10 µg/ml and 0.5-5 µg/ml, respectively. The RP-HPLC method was able to produce well-resolved peaks after 3.0, 8.2 and 20.2 min, in the ranges of 2-10 µg/ml, 0.1-1 µg/ml and 0.05-2 µg/ml, for HQ, HC and TRT, respectively. The obtained A, D1 or peak areas values plotted against the concentration of each of the three components showed linear response in the stated ranges. Both methods were validated in terms of linearity, LOD, LOQ, precision, accuracy and selectivity. Conclusion: Both developed proposed methods were applied for the determination of the active ingredients in the pharmaceutical formulation and the common excipients did not interfere in the analysis. The RP-HPLC method proved to be more sensitive when compared to the applied spectrophotometric method. However, the applied spectrophotometric methods, considered as green analytical chemistry, is a simple, time-saving method that requires minimal use of a hazardous solvent

IDENTIFICATION AND QUANTIFICATION OF PHOSPHODIESTERASE-5 INHIBITORS AS ADULTERANTS IN DIETARY SUPPLEMENTS MARKED FOR SEXUAL ENHANCEMENT IN THE LEBANESE MARKET

Objective: Ultraviolet Visible spectrophotometric was adopted to identify and quantify any adulteration with PDE-5 inhibitors (Sildenafil and Tadalafil) in selected dietary supplements used for sexual enhancement in the Lebanese market Methods: Nine dietary supplements, randomly collected from Lebanese pharmacies, were screened for Sildenafil and Tadalafil using UV-spectrophotometry for both qualitative and quantitative detection. Results: Tadalafil was detected in one sample at a dose of 59 mg/dosage unit, with the maximal recommended dose being 20 mg. Sildenafil was detected in five samples at doses ranging from 11.7 to 188.2 mg/dosage unit, with the maximal recommended dose being 100 mg. Conclusion: This study demonstrates that regular analysis of supposed dietary supplements is needed for more effective quality control and health promotion. The method described for the extraction, identification and quantification of Tadalafil and Sildenafil would be useful for regulatory detection of adulterations

ASSESSMENT OF THE KNOWLEDGE, ATTITUDE, AND PRACTICE TOWARDS EXPIRED DRUG DISPOSAL AMONG THE COMMUNITY IN BEIRUT CITY, LEBANON

The global increase in pharmaceutical spending has led to enhanced international awareness of the unused and expired drug issues due to improper drug disposal\u27s harmful economic, environmental, and health effects. Consequently, the study was conducted to assess the knowledge, attitude, and practice toward expired drug disposal among the community in Beirut City, Lebanon. A cross-sectional, observational, questionnaire-based study was conducted. Data were analyzed using SPSS version 23. The fact that improper disposal of expired medicine affects the environment and health was acknowledged by 70.7% of the 450 participants. Even though 72.2% of the participants knew that the best method for drug disposal was medication disposal boxes, 50.4% did not know about the use of the drug take-back system. Expired drugs were present in 71.1% of the participants’ homes, and 78.9% of the participants discarded them in household garbage. In fact, 53.6% agreed that there is a lack of adequate information on the safe disposal of expired household medicines. This study revealed a lack of proper advice on the safe disposal of expired medicines. Consequently, the government should initiate feasible expired drug programs to educate the public. Improper disposal of expired drugs has a negative impact on the environment. The current study revealed that 78.9% of the participants discards expired drugs in an improper way. Accordingly, actions should be taken to save the planet

RP-HPLC AND CHEMOMETRIC METHODS FOR THE DETERMINATION OF TWO ANTI-DIABETIC MIXTURES; METFORMIN HYDROCHLORIDE-CANAGLIFLOZIN AND METFORMIN HYDROCHLORIDE-GLICLAZIDE IN THEIR PHARMACEUTICAL FORMULATION

Objective: To develop and validate novel more sensitive analytical methods for the concurrent quantification of metformin-canagliflozin and metformin-gliclazide in their bulk forms and in their pharmaceutical preparations. Methods: Two methods were developed based on several chemometric assisted spectrophotometric methods and a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC). The first method applies different spectrophotometric chemometric assisted methods, including ratio difference, derivative ratio and extended ratio subtraction method, while the second method describes a RP-HPLC separation of metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide binary mixtures using a C18 column with a mobile phase consisting of acetonitrile: potassium dihydrogen phosphate (adjusted to pH 3) with sodium lauryl sulphate as additive in the ratio of 30:70 (%v/v) in isocratic elution mode at 1 ml/min. Results: The proposed methods were able to quantify each of the studied drugs in their binary mixtures with high percentage recoveries in both methods. The spectrophotometric methods were able to quantify each of metformin, canagliflozin and gliclazide in the ranges of 2.0-20.0 μg/ml, 1.5-40.0 μg/ml and 2.0-30.0 μg/ml, respectively. The RP-HPLC method produced well-resolved peaks at a retention time of 3.92, 6.92 and 9.10 min in the concentration ranges of 50.0-300.0 μg/ml, 5.0-50.0 μg/ml and 10.0-100.0 μg/ml for metformin, canagliflozin and gliclazide, respectively. The proposed methods were optimized and validated in accordance to the International Conference of Harmonisation (ICH) guidelines in terms of linearity, LOD, LOQ, precision and accuracy. Conclusion: The developed methods were found to be sensitive and reproducible methods for the simultaneous determination of anti-diabetic binary mixtures; metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide. And thus were successfully employed for the quality control analysis of the pharmaceutical formulations of the studied binary mixtures

NOVEL SELECTIVE SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF METHIMAZOLE IN PURE FORM AND IN PHARMACEUTICAL FORMULATION

Objective: To develop and validate new, selective spectrophotometric colorimetric analytical methods for the quantification of methimazole in its pure form and in its pharmaceutical preparations. Methods: Method A is based on the oxidation of methimazole with potassium permanganate in alkaline medium, the manganate ion produced was measured at λmax= 610 nm. Method B is a kinetic determination of methimazole using fixed-time method based on the oxidation of methimazole using known excess of cerium (IV) nitrate in acidic medium and assessing the unreacted Ce (IV) by adding a fixed amount of methyl orange and measuring the absorbance of the resultant solution at λmax=507 nm which is equivalent to the unreacted methyl orange. The reaction conditions and analytical parameters are investigated and optimized. Method validation was carried out according to ICH guidelines in terms of linearity, LOD, LOQ, precision, and accuracy. Results: Beer’s law is obeyed in the range of 1.50–15.00 μg/ml for method A and 0.25–3.00 μg/ml for method B. The developed methods were subjected to the detailed validation procedure. The proposed spectrophotometric methods were applied for the determination of the methimazole in its pure form and in its pharmaceutical formulation. The percentage recoveries were found to be 100.82 % and 99.85 % in the pharmaceutical formulation for the two proposed methods, respectively. Conclusion: Both developed spectrophotometric methods, considered as green analytical chemistry, were found to be novel, highly selective and can be applied for the quality control of methimazole in its pure form and in its pharmaceutical formulation based on the simplicity, applicability of the parameters, accessibility of the reagents employed and reasonably low time of analysis

NOVEL FAST ANALYTICAL METHODS FOR THE ANALYSIS OF FLUOXETINE IN PURE AND PHARMACEUTICAL DOSAGE FORM

Novel and accurate analytical methods were developed and validated for the characterization of Fluoxetine in its pure and pharmaceutical dosage form Prozac®. Fluoxetine was determined by IBA techniques (PIGE, PIXE and RBS). It has been also analyzed spectrophotometrically at 610 nm after oxidation with potassium permanganate in alkaline medium. In addition, Fluoxetine was kinetically determined using the initial rate method, the fixed absorbance method and the fixed time method. Moreover, a Gas chromatography - mass spectrometry technique is proposed for the investigation of Fluoxetine without a prederivatization phase. The spectrophotometric method was performed with a concentration array of 2-10 μg/mL at 610 nm and a regression coefficient (r) of 0.996. The fixed time method was the most suitable one to determine Fluoxetine with correlation coefficient value (r) of 0.9966. The Gas chromatography - mass spectrometry investigated the drug in a concentration range of 20-100 μg/mL and a regression coefficient (r) of 0.999. IBA analysis presented a precision of less than 3% and a very low limit of detection. Consequently, these proposed methods would be useful tools for determining Fluoxetine as all the assay results exposed satisfactory sensitivity, accuracy and reproducibilit

IN VITRO EQUIVALENCE STUDY OF GENERIC METFORMIN HYDROCHLORIDE TABLETS UNDER BIOWAIVER CONDITIONS

Background: Generic drugs are smarter alternative to expensive brands, it is bio- equivalent formula of any branded drug. FDA approved that generic drugs are the safest to consume, the medicines meet the similar manufacturing standards followed while producing an innovator drug, however, the color, shape, taste and packaging of generics is different from the innovator product. In short, a generic drug should be bioequivalent to its brand counterpart. Metformin was initially marketed under the name of Glucophage®, and now the market is loaded by generics of different origin, and price variability. Method: Our study was conducted to determine whether metformin generics are bioequivalent to the innovator drug Glucophage®. In-vitro bioequivalence testing under Biowaiver conditions can predict bioequivalence in a safe, fast, and less expensive method. Thus, study was performed on Metformin tablets to assess whether generics are bioequivalent to the innovator and hence be interchangeable. Results: The quality control results of the thickness, hardness, friability, disintegration, weight uniformity, content uniformity, and assay showed that most metformin tablets complied with the USP 34 NF29 2011 specifications. Dissolution testing under biowaiver conditions showed different results. All tablets of the generics and innovator Glucophage® were able to dissolve by more than 85% within 15 min. Two generics were bioequivalent to the innovator Glucophage® having f2≥ 50 in the three dissolution media. The rest of generics showed variable results. Conclusion: Generics of metformin varied in their bioequivalency to the innovator Gluocophage®. This variation could be explained by different excipients, and manufacturing conditions. In-vivo bioequivalence testing should be conducted to confirm that the innovator could be safely interchangeable with the brand and this variation won’t affect the safety and efficacy of the drug

Simple Spectrophotometric Methods for Determination of Tenofovir Fumarate and Emtricitabine in Bulk Powder and in Tablets

Two simple and selective methods were developed for the simultaneous determination of tenofovir fumarate (TEN) and emtricitabine (EMT) in combined tablets. The first method involves the application of first derivative spectrophotometry where the first derivative amplitudes were measured at 298.5 nm for determination of EMT in presence of TEN. The second method involves first derivative of ratio spectra spectrophotometry where the amplitudes at 251.5 nm have been used for quantitation of TEN in the presence of EMT. Different variables affecting each method were carefully investigated and optimized. Reliability and analytical performance of the proposed methods, including linearity, range, precision, accuracy, detection, and quantitation limits, were statistically validated. The methods were successfully applied for the determination of EMT and TEN in laboratory-prepared mixtures and in their combined tablets