Ganesa Sundararajan Subramanian

A study of rivastigmine liposomes for delivery into the brain through intranasal route

A study of rivastigmine liposomes for delivery into the brain through intranasal route The present study is mainly aimed at delivering a drug into the brain via the intranasal route using a liposomal formulation. For this purpose, rivastigmine, which is used in the management of Alzheimers disease, was selected as a model drug. Conventional liposomes were formulated by the lipid layer hydration method using cholesterol and soya lecithin as lipid components. The concentration of rivastigmine in brain and plasma after intranasal liposomes, free drug and per oral administration was studied in rat models. A significantly higher level of drug was found in the brain with intranasal liposomes of rivastigmine compared to the intranasal free drug and the oral route. Intranasal liposomes had a longer half-life in the brain than intranasally or orally administered free drug. Delivering rivastigmine liposomes through the intranasal route for the treatment of Alzheimers disease might be a new approach to the management of this condition. Liposomi rivastigmina za isporuku u mozak intranazalnim putem Glavni cilj rada je razvoj liposoma za intranazalnu primjenu za isporuku lijeka u mozak. U tu svrhu izabran je rivastigmin kao modelni lijek koji se upotrebljava u terapiji Alzheimerove bolesti. Liposomi su pripravljeni metodom hidratacije lipidnog sloja koristeći kolesterol i lecitin iz soje kao lipidne komponente. Praćena je koncentracija rivastigmina u mozgu i plazmi nakon intranazalne i peroralne primjene liposoma i slobodnog lijeka. S intranazalnim liposomima rivastigmina postignuta je značajno veća koncentracija lijeka u mozgu. Osim toga intranazalni liposomi imaju dulje vrijeme poluživota u mozgu. Intranazalna primjena liposoma rivastigmina mogla bi predstavljati novi pristup terapiji Alzheimerove bolesti.

Simultaneous estimation of paracetamol and domperidone in tablets by reverse phase HPLC method

A simple, fast, precise and accurate liquid chromatographic method was developed for the simultaneous estimation of paracetamol and domperidone in combined dosage forms. This combination is used for antiemetic and pain associated with gastrointestinal disorders. Drugs are chromatographed on a reverse phase Kromasil C18 column using a mobile phase, 20 mM phosphate buffer (pH 7.0±0.1) and acetonitrile in the ratio of 60:40%v/v. Diclofenac potassium was used as an internal standard. The retention time of paracetamol, domperidone, and diclofenac potassium was 2.94, 8.30, 5.67 min, respectively. The validation of the proposed method was also carried out. The method was found to be linear (r>0.99), precise (%RSD: 0.49% for paracetamol and 0.89% for domperidone), accurate (overall average recovery yields: paracetamol 99.1% and domperidone 98.36%) and selective. Due to its simplicity and accuracy the proposed method can be used for routine quality control analysis of these drugs in combined dosage form.

Determination of telmisartan by HPTLC — A stability indicating assay

Hypertension is the most prevalent disease worldwide and requires constant monitoring. The trend in cardiovascular drug research has been to develop new compounds acting on very specific targets, for example cell-surface receptors. Angiotensin II receptors are long-acting and well tolerated. Telmisartan (Figure 1) is a new benzimidazole derivative antagonist of the subtype angiotensin II (AT-II) receptor intended for treatment of essential arterial hypertension. It is highly safe with excellent efficacy and few side-effects [1, 2].

Stability-indicating HPTLC determination of imatinib mesylate in bulk drug and pharmaceutical dosage form

A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of imatinib mesylate both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (6:4, v/v). The system was found to give compact spot for imatinib mesylate (R(f) value of 0.53+/-0.02). Densitometric analysis of imatinib mesylate was carried out in the absorbance mode at 276 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9966+/-0.0013 with respect to peak area in the concentration range 100-1000 ng per spot. The mean value+/-S.D. of slope and intercept were 164.85+/-0.72 and 1168.3+/-8.26 with respect to peak area. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 10 and 30 ng per spot, respectively. Imatinib mesylate was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and heat conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and heat. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of imatinib mesylate in bulk drug and dosage forms.

Stability-Indicating HPTLC Determination of Rivastigmine in the Bulk Drug and in Pharmaceutical Dosage Forms

A. simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic method for analysis of rivastigmine in the bulk drug and in a capsule formulation has been established and validated. Chromatographic separation was achieved on aluminum-backed silica gel 60F254 HPTLC plates with chloroform-methanol 4:6 (v/v) as mobile phase. Densitometric analysis of rivastigmine was performed in absorbance mode at 210 nm. The method gave a compact spot for rivastigmine (RF 0.53 ± 0.02) and was shown to enable excellent separation of a degradation product of rivastigmine (RF 0.32 ± 0.02). The method was validated for accuracy, precision, linearity, recovery, limits of detection and quantitation, and robustness. Good linearity was observed in the concentration range 200-1600 ng per spot; the correlation coefficient was 0.9916 ± 0.008. The limits of detection and quantitation were 30 and 100 ng per spot, respectively. Rivastigmine was subjected to alkaline hydrolysis and high humidity and found to degrade under these conditions. Statistical analysis proved the method was reproducible, specific, and accurate. The method is stability indicating; because it is economical it can be used for routine analysis of the bulk drug and pharmaceutical formulations.

High-performance thin-layer chromatographic analysis of bicalutamide in bulk drug and liposomes

A sensitive, accurate, precise, and specific high-performance thinlayer chromatographic (HPTLC) method for analysis of bicalutamide in the bulk drug and in a liposomal formulation containing cholesterol and lecithin and other surfactants has been established and validated in accordance with ICH guidelines. HPTLC on aluminum foil-backed silica gel 60F-254 plates with toluene-ethyl acetate 4.5:5.5 (v/v) as mobile phase gave compact bands for bicalutamide (RF 0.45). Leflunomide (RF 0.85) was used as internal standard. Densitometric analysis of bicalutamide was performed in absorbance mode at 273 nm. The method was validated for accuracy, precision, linearity, robustness, and limits of detection and quantitation. The method is specific, selective, and free from matrix interferences at the RF of bicalutamide and the internal standard. Regression data for the calibration plots were indicative of a good linear relationship (correlation coefficient 0.9994 ± 0.002) between response and amount of bicalutamide in the concentration range 200–1600 ng per band. The limits of detection and quantitation were 50 and 200 ng per band, respectively.

High-Performance Thin-Layer Chromatographic Determination of Etoricoxib in the Bulk Drug and in Pharmaceutical Dosage Form

A sensitive, accurate, precise, and stability-indicating high-performance thin-layer chromatographic method has been established and validated for analysis of etoricoxib in both bulk drug and formulations. Chromatography is performed on aluminum-backed silica gel 60F254 plates with toluene-1,4-dioxane-methanol 8.5:1.0:0.5 (v/v) as mobile phase. This system furnished compact bands for etoricoxib (RF 0.24). Rofecoxib (RF 0.38) was used as internal standard. Densitometric analysis of etoricoxib was performed in absorbance mode at 235 nm. Linear regression data for the calibration plots showed there was a good linear relationship between response and amount of etoricoxib in the range 100-1500 ng per spot; the correlation coefficient was 0.9922 ± 0.001. The mean values of the slope and intercept of the plot were 280.14 ± 0.26 and 320.01 ± 0.22, respectively. The method was validated for precision, accuracy, robustness, and recovery. The limits of detection and quantitation were 30 and 100 ng per spot, respectively. The drug undergoes degradation when subjected to neutral, acidic, or basic hydrolysis, oxidation, or dry heat treatment, but the degradation products were well separated from the drug (different RF values). Because the method could effectively separate the drug from its degradation products it can be regarded as stability-indicating.

Dissolution development of valdecoxib tablets

Valdecoxib is a nonsteroidal antiinflammatory drug, and it is listed in class 2 of biopharmaceutic classification of drugs. Valdecoxib is a poorly water-soluble and highly permeable drug. In the present study a new dissolution medium was developed, as there is no official dissolution medium available in the literature. The composition of the dissolution medium was selected on the basis of solubility data at 37°. Solubility data revealed that addition of surfactant may be suitable as dissolution medium. The concentration of 0.6% w/v sodium lauryl sulphate in water could be a suitable dissolution medium. The discriminating power of the selected dissolution medium (0.6% sodium lauryl sulphate in water) relative to the other dissolution mediums was evaluated. The selected dissolution medium was used for the evaluation of valdecoxib tablets.

Stability-Indicating HPTLC Determination of Capsaicin in the Bulk Drug

A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for analysis of capsaicin in the bulk drug has been developed and validated. The method employs aluminum TLC plates precoated with silica gel 60F254 as stationary phase. The mobile phase was toluene-ethyl acetate 6:4 (v/v). A compact spot was obtained for capsaicin (RF 0.38 ± 0.02). Densitometric analysis of capsaicin was performed in absorbance mode at 280 nm. Regression analysis of calibration data revealed a good linear relationship (r2 > 0.9936) for peak-area data in the concentration range 100-1000 ng per band. The method was validated for accuracy, precision, linearity, limit of detection, limit of quantitation, and robustness. The limits of detection and quantitation were 20 and 60 ng per band, respectively. Capsaicin was subjected to acidic and alkaline hydrolysis, oxidation, and thermal degradation. The drug undergoes degradation under acidic, basic, and oxidizing conditions and at elevated temperatures. Statistical analysis proved the method enables precise, selective, and accurate analysis of capsaicin. The method can be used for identification and quantitative analysis of capsaicin in the bulk drug.