HPLC methods dosage forms

Gradient HPLC Yes/No Complex Low Receiving site has extensive familiarity with other products and methodologies of this compound, but not with this dosage form, e.g. tablet product/method is established, but no experience of this oral liquid product. Method has a good history of reproducible performance. Method confirmation... 

For a liquid or semi-solid pharmaceutical dosage form, it is crucial to include a preservative in the formulation. Commonly used preservatives in these systems include sodium benzoate, EDTA, sorbic acid, and parabens. A generic HPLC method is also recommended for the preservatives used in liquid formulations for routine monitoring to ensure the stability of the preservative itself and it must be validated specific to its use with the dosage form. (See chapters on Sample Preparation and Method Development.)... 

Reliable quality control in the field of pharmaceutical analysis is based on the use of valid analytical methods. For this reason, any analytical procedures proposed for a particular active pharmaceutical ingredient and its corresponding dosage forms shonld be validated to demonstrate that they are scientifically sonnd nnder the experimental conditions intended to be used. Since dissolntion data reflect drng prod-net stability and quality, the HPLC method used in snch tests shonld be validated in terms of accuracy, precision, sensitivity, specificity, rngged-ness, and robustness as per ICH guidelines. 

El-gizawy reported the analysis of diloxanide furoate in its dosage forms by a HPLC method [40]. Furazol tablets containing 200 mg of metronidazole and 250 mg of diloxanide furoate were treated with 50 mL of methanol, sonicated for 10 minutes, and diluted to 100 mL with methanol. A portion of the resulting solution was centrifuged, and a 20 pL portion of the clear supernatant solution diluted to 10 mL with the mobile phase. This process yielded a final analyte concentration equivalent to 5 pg/mL. 20 pL aliquots of the solution were annualized by HPLC using a stainless steel column (10 cm x 4.6 mm) packed with Cyclobond I. The mobile phase consisted of 13 7 0.05 M phosphate buffer (pH 7) methanol (flow rate of 1 mL/min), and detection was performed at 254 nm. 

Rao et al. reported a high performance liquid chromatographic method to determine diloxanide furoate and metronidazole in single and in combined dosage forms [41]. A 30 mg equivalent of diloxanide furoate and 25 mg of metronidazole (either as the bulk drug substances or in powdered tablets) was dissolved in methanol, amidopyrine added as the internal standard, and the mixture analyzed by HPLC at room temperature. The analytical column (30 cm x 3.9 mm) consisted of p-Bondapak Cig, with 9 9 1 1 methanol water 0.05 M KH2PO4 0.05 M NaH2P04 as the mobile phase. The flow rate was 1 mL/min), and detection was performed at 254 nm. 

For formulated products an essential analysis is the assay for API content. This is usually performed by HPLC, but Raman spectroscopy can offer a quantitative analytical alternative. These applications have been extensively researched and reviewed by Strachan et al. [48] and provide over 30 literature references of where Raman spectroscopy has been used to determine the chemical content and physical form of API in solid dosage formulations. As no sample preparation is required the determination of multiple API forms (e.g. polymorphs, hydrates/solvates and amorphous content) provides a solid state analysis that is not possible by HPLC. However, as previously discussed sampling strategies must be employed to ensure the Raman measurement is representative of the whole sample. A potential solution is to sample the whole of a solid dosage form and not multiple regions of it. As presented in Chap. 3 the emerging technique of transmission Raman provides a method to do just this. With acquisition times in the order of seconds, this approach offers an alternative to HPLC and NIR analyses and is also applicable to tablet and capsule analysis in a PAT environment. 

D.A. Shah, K.K. Bhatt, R.S. Mehta, M.B. Shankar, S.L. Baldania, T.R. Gandhi, Development and validation of a RP-HPLC method for determination of atorvastatin calcium and aspirin in a capsule dosage form, Indian J. Pharm. Sci. 69 (2007) 546-547. 

N. Jain, R. Raghuwanshi, D. Jain, Development and validation of RP-HPLC method for simultaneous estimation of atorvastatin calcium and fenofibrate in tablet dosage forms, Indian J. Pharm. Sd. 70 (2008) 263-265. 

TABLE 2.5 Summary of HPLC methods used to analyze clopidogrel bisulfate in bulk drug substance and pharmaceutical dosage forms... 

El-Sherif et al. [79] developed and validated a reversed-phase HPLC method for the quantitative determination of omeprazole and two other proton pump inhibitors in the presence of their acid-induced degradation products. The drugs were monitored at 280 nm using Nova-Pak Ci8 column and mobile phase consisting of 0.05 M potassium dihydrogen phosphate-methanol-acetonitrile (5 3 2). Linearity range for omeprazole was 2-36 fig/ml. The recovery of omeprazole was 100.50 0.8%, and the minimum detection was 0.54 /zg/ml. The method was applied to the determination of pure, laboratory prepared mixtures, and pharmaceutical dosage forms. The results were compared with the official USP method for omeprazole. 

H. P. Yuan and D. C. Locke, HPLC method for the determination of diphenhydramine in liquid and solid drug dosage forms and its application to stability testing, Drug Dev. Ind. Pharm., 77 2319 (1991). 

J. E. Kountourellis, C. K. Markoupoulou, and P. E. Georgako-poulos, An HPLC method for the separation and simultaneous determination of antihistamines, sympathomimetic amines and dextromethorphan in bulk dry material and dosage forms, Anal. Lett., 23 883 (1990). 

T. Kubala, B. Gamblhir, and J. I. Borst, A specific stability indicating HPLC method to determine diclofenac in raw materials and pharmaceutical solid dosage forms, Drug Dev. Ind. Pharm, 19 749(1993). 

HPLC is the most frequently used technique for the analysis of spironolactone as the bulk drug, in its dosage forms, or in biological fluids. The reported HPLC methods are summarized in Table 6. 

Schieffer, G. 2000. Validated HPLC method for caffeic-acid derivatives and alkylamides of Echinacea solid-dosage forms using a single extraction procedure. J. Am. Nutraceutical Assoc. 3, 67-81. 

Hassib et al. developed two chromatographic procedures for the simultaneous determination of benazepril hydrochloride and hydrochlorothiazide in laboratory made mixtures, and in pharmaceutical dosage forms (Cibadrex tablets) using reversed phase HPLC and TLC methods [24]. For reversed phase HPLC, a very sensitive, rapid, and selective method was developed. The linearity ranges were 32-448 ng/ 20 pL and 40-560 ng/20 pL for benazepril hydrochloride and hydrochlorothiazide, respectively. The corresponding recoveries were 99.38 1.526 and 99.2 1.123. The minimum detection limits were 7 ng/20 pL for benazepril and 14 ng/20 pL for hydrochlorothiazide. The method could be successfully applied for the determination of laboratory made mixtures and for pharmaceutical dosage forms. The results obtained were compared with those obtained by a spectrophotometric method. 

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