C. Bethea

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.

EFFECT OF EXCIPIENTS ON THE STABILITY OF LEVOTHYROXINE SODIUM TABLETS

Levothyroxine sodium tablets from two different manufacturers were analysed using the USP‐NF method of analysis, a stability‐indicating high pressure liquid chromatographic (HPLC) procedure. The results indicate that one particular manufacturers 0.2‐mg pink tablets contain some excipient(s) which act as a catalyst to hasten decomposition after extraction of levothyroxine for analysis. The same tablets from a different batch showed an additional long peak in the chromatogram, which indicated that the excipient(s) may have been changed. The same manufacturer has also used three different types of bottles/lids for the same product during the last year. Good manufacturing practice requires that new compatibilities/ stability studies be conducted to assure the quality of the product. Ongoing stability studies are required by the Food and Drugs Administration (FDA). The use‐life of 0–2‐mg pink tablets of this manufacturer may be short.

Stability of piperacillin sodium in the presence of tazobactam sodium in 5% dextrose and normal saline injections

The stability of piperacillin sodium in the presence of tazobactam sodium in 5% dextrose and normal saline i.v. admixtures has been determined using a modified stability‐indicating high performance liquid chromatography assay method reported in the literature. The solutions were stored at room and refrigerator temperatures in plastic bags. They remained clear throughout the study although the pH values decreased slightly during storage. The solutions were stable for 2 days at 25d̀C and for 28 days at 5d̀C. Tazobactam sodium appears to have a slight adverse effect on the stability of piperacillin sodium.

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.

Stability of metronidazole benzoate in suspensions

A stability‐indicating HPLC assay method has been developed to quantify metronidazole benzoate in suspensions. A study of the stabilities of two suspensions (16‐0 mg/ml) of metronidazole benzoate in commercially available vehicles, Ora‐Plus and a mixture of Ora‐Plus and Ora‐Sweet, showed that both suspensions were stable for at least 90 days at room temperature. The mobile phase required to elute metronidazole benzoate contained 40% acetonitrile versus approximately 10% for the free base. The solubility of the ester in water at 25d̀C was found to be approximately 0‐1 mg/ml versus 10 mg/ml for the free base. The ester did not hydrolyse significantly to the free base after storage for 8 h at 37d̀C in simulated gastric fluid, and 5 h at 37d̀C in simulated intestinal fluid. The bitter tasting metronidazole may not be satisfactorily substituted with its tasteless ester in the treatment of local gastrointestinal infections.

Quantitation of Nizatidine in Capsules Using High-Performance Liquid Chromatography

AbstractA stability-indicating high-performance liquid chromatography method for the quantitation of nizatidine in capsules has been developed. The method is accurate and precise with a percent relative standard deviation of 0.34 based on 6 readings. A number of inactive ingredients present in the capsules did not interfere in the assay procedure. The recovery from the synthetic mixtures was quantitative. The extraction procedure from the capsules is very simple. The drug appears to be very sensitive to bases (such as sodium hydroxide) since 100% of the drug decomposed on boiling for 35 minutes. The drug was very stable when boiled with sulfuric acid.

Quantitation of Flurbiprofen in Tablets Using High Performance Liquid Chromatography

AbstractA stability-indicating high-performance liquid chromatography method for the quantitation of flurbiprofen in tablets was developed. The method is accurate and precise with a percent relative standard deviation of 0.7 based on 8 readings. A number of inactive ingredients present in the tablets did not interfere with the assay procedure. The extraction procedure from the tablets is very simple. The recovery from the synthetic mixtures was quantitative. The drug appears to be very sensitive to strong acids and bases since a 5 minute boiling caused the degradation of drug (100 %) in both the solutions

CHEMICAL STABILITIES OF FAMOTIDINE AND RANITIDINE HYDROCHLORIDE IN INTRAVENOUS ADMIXTURES

The chemical stabilities of famotidine and ranitidine hydrochloride solutions in 5% dextrose and 0·9% sodium chloride injections have been studied using high‐performance liquid chromatographic methods (HPLC). Both the drugs were stable for at least 15 days (loss in potency of less than 10%) at 25°C and 63 days at 5°C. Both drugs were comparatively less stable in 5% dextrose injection than in 0·9% sodium chloride injection. The loss in the potency of phenol, which is added as a preservative to ranitidine hydrochloride injection, was significant in both the vehicles. However, the addition of preservative in a single dose vial is not considered necessary.

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.