Y. Pramar

Development of a stable oral liquid dosage form of spironolactone

A clear, stable, oral liquid dosage form of spironolactone has been developed. Solubility profiles of spironolactone were obtained in several co‐solvent blends. Using this data, a co‐solvent blend containing polyethylene glycol 400 (30% v/v), propylene glycol (10% v/v), glycerin (10% v/v) and ethyl alcohol (10% v/v) was used to solubilize spironolactone at a concentration of 2 mg/ml. The final formulation contained sweetening agents (sucrose, saccharin sodium), flavours (cherry, sweet), a desensitizing agent (menthol), a dye (FD&C Red #40) and a preservative (benzoic acid) to incorporate the desired organoleptic and preservative properties. A phosphate buffer was used to maintain a pH value of 4.5 (pH of maximum stability as reported earlier) to minimize hydrolysis. The final dosage form was stable for at least 93 days at 40°C (loss of potency less than 4%). According to FDA guidelines, a tentative expiry date of 2 years at 25°C is justifiable.

Stability of captopril in some aqueous systems

A stability‐indicating high performance liquid chromatographic method has been proposed to quantify captopril. The method has been used to determine the stability of captopril in oral liquid dosage forms prepared from either commercially available tablets or powder. The dosage forms in water were more stable than when the vehicle was a syrup. Furthermore, the dosage form prepared using powder in water was more stable than when tablets were used. While the decomposition of captopril followed first‐order equation when the dosage forms were prepared in syrup (in two of the three solutions studied), this equation was not followed when water was the vehicle. This is probably due to an uncontrolled factor, oxygen, because captopril is very sensitive to oxidation. Captopril solution prepared in water using tablets was stable for about 20 days when stored at 5°C, and that prepared using powder in water was stable for about 27 days. One commercial syrup hastened the process of decomposition with an additional unidentified product of decomposition.

STABILITY OF ACYCLOVIR SODIUM IN DEXTROSE AND SODIUM CHLORIDE INJECTIONS

The chemical stability of acyclovir sodium in dextrose 5% w/v and sodium chloride 0·9% w/v injections has been studied using a stability‐indicating high‐pressure liquid chromatographic (HPLC) method. The drug appears to be very stable in both admixtures. There was no decomposition after 37 days of storage at 25°C or 5°C. The manufacturer‐recommended expiry date of 24 h at 25°C is too conservative. The solutions were clear throughout the study period and the pH values had decreased slightly in both the solutions. Acyclovir appears to be very stable on the alkaline side of the pH range and less so on the acidic side. There was no loss in the potency of acyclovir when mixed with dobutamine and dopamine.

Quantitation of spironolactone in the presence of canremone using high-performance liquid chromatography

AbstractTwo stability-indicating high-performance liquid chromatography methods have been developed to quantify spironolactone in the presence of its product(s) of decomposition. Both methods are accurate and precise with percent relative standard deviation of 0.7 based on 5 readings using microC18 column and 0.9 using microphenyl column. By using different wavelengths, the sensitivity of the methods to quantify spironolactone or canrenone (the major product of decomposition of spironolactone) can be increased many times. Spironolactone appears to be relatively stable between pH values of about 3.4-5.2. In the acidic pH, the decomposition is slower than on the basic side of the pH. Even at pH 7.3, the decomposition was about 3.1 times faster than at pH 2.3.

Quantitation of fluoxetine hydrochloride in capsules using high-performance liquid chromatography

AbstractA stability-indicating high-performance liquid chromatographic method for the quantitation of fluoxetine hydrochloride in capsules (the only dosage form available) has been developed. The method is accurate and precise with a percent relative standard deviation of 1.04 based on 6 readings. An excellent separation of fluoxetine from methyltestosterone (the internal standard) was achieved, and sharp peaks were obtained by adding acetic acid to the mobile phase. The inactive ingredients present in the capsule powder did not interfere with the assay procedure. The recovery of fluoxetine from the synthetic mixtures was quantitative. The drug appears to be very stable in the acidic medium and highly susceptible to degradation in the basic medium.

Chemical stability of cefotetan disodium in 5% dextrose and 0.9% sodium chloride injections.

The chemical stability of cefotetan disodium in 5% dextrose and 0.9% sodium chloride injections has been studied using a stability‐indicating high‐pressure liquid chromatographic (HPLC) assay method. The drug appears to be relatively unstable at 25oC (expiry time 2 days), compared with at least 41 days at 5oC and at least 60 days at ‐10oC. Thawing the frozen samples in a microwave (90 s) did not cause any significant decomposition. The manufacturers recommended expiry time of 4 days at 5oC and at least 7 days at ‐10oC is very conservative. The HPLC method developed is accurate and precise with a relative percentage standard deviation of 1.7 based on six readings. The method appears to be stability‐indicating as the samples decomposed under drastic conditions had almost no drug left and new peaks were observed in the chromatograms.

STABILITIES OF DOBUTAMINE, DOPAMINE, NITROGLYCERIN AND SODIUM NITROPRUSSIDE IN DISPOSABLE PLASTIC SYRINGES

The solutions of dobutamine hydrochloride (5 mg/ml), dopamine hydrochloride (4mg/ml), nitroglycerin (1 mg/ml) and sodium nitroprusside (1 mg/ml) in dextrose 5% injection were stable for 24 h when stored at 25°C in 60‐ml plastic syringes. For sodium nitroprusside, the syringes must be wrapped with aluminium foil (provided by the manufacturer), otherwise the loss in potency is very high (22%). There was no change in the pH values of dobutamine and dopamine solutions as well as sodium nitroprusside solutions in the prewrapped syringes. However, the pH value of nitroglycerin solutions decreased to 4·3 from 4·6 and that of sodium nitroprusside solutions in unwrapped syringes from 4·2 to 3·5; these solutions had discoloured. The chromatogram also showed new peaks from the products of decomposition. The physical appearances of the other solutions did not change.

Quantitation of Scopolamine Hydrobromide When Adsorbed Onto Microcrystalline Cellulose and Sodium Carboxymethylcellulose in Tablets

AbstractBoth scopolamine and lidocaine (the internal standard) got adsorbed onto sodium carboxymethylcellulose and microcrystalline cellulose, which are commonly added to the tablets/capsules as excipients. In one tablet formula which contained both adsorbents, about 42% of scopolamine and 45% of lidocaine got adsorbed. Sodium carboxymethylcellulose by itself, adsorbed both drugs about 26.2 times more than microcrystalline cellulose, when compared on the basis of same weights. If hydrochloric acid was used in the extraction procedure, both scopolamine and lidocaine got desorbed and recovery was quantitative.

Important Information for Readers of High-Performance Liquid Chromatography Literature

AbstractImportant information for developing an internal standard for high-performance liquid chromatography has been presented in a tabular form. If acetonitrile is substituted for methanol, the column lives are longer and costly repairs of the chromatograph are not needed that often. Approximately 1% of acetonitrile can be substituted for 2% of methanol.

Quantitation of 5-Flucytosine in capsules using high-pressure liquid chromatography

AbstractA stability-indicating reversed phase HPLC method for the quantitation of 5-flucytosine in capsules (the only dosage form available) has been developed. The method requires the use of a mobile phase without any counterion and the samples can be assayed at room temperature. The method is simple, reproducible, precise and accurate with percent relative standard deviation of 0.77 based on 6 readings. There was no interference from the excipients present in capsules and from fluorouracil (the major product of decomposition of 5-flucytosine). The recovery of 5-flucytosine from the synthetic mixtures was quantitative. A simple extraction procedure for 5-flucytosine from the capsules has been developed.