Nitrofurantoin Tablets Research Articles

Formulation of Nitrofurantoin Tablets Fulfilling the Pharmacopoeial Specifications

The USP XXII specifies that the disintegration time for nitrofurantoin tablets must be not less than 30 minutes, not less than 25% of the drug is dissolved in 60 minutes and not less than 85% is dissolved in 120 minutes. These specifications were done to minimize the side effects and to achieve a proper bioavailability for the drug.On testing the market tablet preparation (Furadantin), it was found that it does not fit to the [JSP specifications, Nine nitrofurantoin tablet formulations were then tried and each was studied for disintegration time and % dissolution in the first and second hours. The best formula was found to be consisted of adding 2% of collodion in 40% of the starting granules, coated with 4% CAP and adding another 2% of collodion to the remaining 60% of the granules.

High–performance liquid chromatographic determination of nitrofurantoin in plasma

SUMMARY A reversed–phase high–performance liquid chromatographic method for the analysis of nitrofurantoin in rabbit plasma was developed. Acetanilide was used as the internal standard. The chromatography was performed using a C–18 column; the mobile phase consisted of 75:25 water to methanol; a flow rate of 09 ml/min; and UV detection at 270 run. Retention times were 58 and 101 min for nitrofurantoin and acetanilide, respectively. Recovery of nitrofurantoin added to plasma in the concentration range of 005–5 μg/ml was found to be greater than 92%. This procedure was used for the analysis of plasma samples collected over time following the oral administration of nitrofurantoin tablets to rabbits.

Nitrofurantoin Excretion in Human Milk

Six lactating white healthy women (26-36 years old, weighing 45-58 kg) were treated with 50 mg nitrofurantoin tablets, a urinary antiseptic. They received either 50 mg (group I; n = 3) or 100 mg (group II; n = 3) 3 times a day (09.00, 16.00, 19.00 h) for 24 h, 2-5 days after the delivery of a full-term neonate. The study was performed on the 4th dose at 09.00 h just before breakfast. Milk samples were collected before, 3 and 6 h after the nitrofurantoin administration with an Egnell SMB breast pump. The complete milk samples were collected from each breast, and pooled. 5 ml venous blood samples were drawn before, 1, 2, 3 and 6 h after nitrofurantoin administration. Plasma and milk nitrofurantoin concentrations were measured by HPLC. Apparent elimination half-life and apparent plasma clearance were the same in both groups, 0.8 +/- 0.09 h and 27.6 +/- 5.57 l/h, respectively. Nitrofurantoin was not detectable in the milk just before the 4th administration. The amount excreted in the milk within 6 h after nitrofurantoin administration was 22-57 micrograms (I) and 61-284 micrograms (II) which represents 0.05-0.11% (I) and 0.06-0.28 (II) of the nitrofurantoin dose. The nitrofurantoin concentration ratio of the breast milk to the plasma collected at 3 h was 2.2 +/- 1.2 (I) and 2.3 +/- 1.6 (II). These results show that nitrofurantoin excretion in human milk is low: below 0.12 (I) and 0.29% (II). It suggested that breast-fed newborn infants from mothers treated with nitrofurantoin would be exposed to small amounts of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging of nitrofurantoin tablets containing Carbopol 934 as a binder

This paper reports the effects of temperature, humidity and storage time on the hardness and dissolution rate of four nitrofurantoin tablet formulations containing Carbopol 934 as binder. In dissolution tests none of the four formulations complied with USP XXI Ed. assay for nitrofurantoin tablets when freshly made, but all did after six months' storage. In view of these alterations in dissolution rate, it seems possible that the age of the tablets used may have been a cause of earlier failures to find in vivo-in vitro correlations for nitrofurantoin. It is recommended that in future in vivo and in vitro studies be carried out with tablets of various ages if Carbopol 934 is employed as sustained release matrix or binder.

Effect of storage on nitrofurantoin solid dosage forms

Storage under adverse conditions of temperature and humidity is not uncommon in many parts of the world. Packages used for the dispensing of medications are often less than adequate. These conditions may adversely affect the quality of pharmaceutical preparations (Gouda et al., 1980; York, 1977). While changes in the chemical stability of drugs in their dosage forms dre usually easily detected, changes in biopharmaceutical properties may pass unnoticed. Nitrofurantoin, a urinary tract antibacterial drug, has a potential for bioavailability problems. Formulation factors, mainly particle size, affect dissolution rate, bioavailability in humans and incidence of side-effects (Cadwallader et al., 1975). The USP XX monograph for nitrofurantoin tablets requires not less than 25% of the labeled amount of drug to dissolve in 60 min in a pH 7.2 phosphate buffer. The objectives of the present study are to determine the effect of storage on the dissolution of nitrofurantoin tablets and capsules and to assess any bioavailability changes associated with storage. Two brands of nitrofurantoin capsules containing macroor microcrystals and a tablet were stored in original blister packs, in child-proof vials and in plastic bags. The storage conditions adopted were 40°C/79W relative humidity (R.H.), 25”C/79% R.H. and 40°C/31W R.H. Samples were taken at various time intervals and the drug content, weight variation and dissolution at 3j”C in a pH 7.2 phosphate buffer (USP XX) were determined. A limited bioavailability study based on determination of urinary excretion of unchanged drug was also carried out. Administration of stored (in plastic bags for 10 weeks at 40°C/79% R.H.) and unstored capsules under non-fasting conditions (Bates et al., 1974) to two healthy volunteers was performed in a cross-over design. W rine samples were collected at various time intervals and analyzed for nitrofurantoin (Conklin and tlollifield, 1965).

In vivo-in vitro Correlations with a Commercial Dissolution Simulator I: Methenamine, Nitrofurantoin, and Chlorothiazide

Dissolution profiles were determined for nine methenamine, 14 nitrofurantoin, and six chlorothiazide dosage forms using a dissolution simulator. Various in vivo-in vitro correlations were examined. The best correlation for methenamine was between the maximum urinary excretion rate and the time for 15% dissolution. A good correlation for the 50-mg nitrofurantoin tablets was also found between cumulative percent of drug excreted in 12 hr and the percent dissolved in 1 hr. There were no significant correlations for the 100-mg nitrofurantoin dosage forms. Good correlations were also observed for the 250- and 500-mg chlorothiazide tablets between the percent of drug dissolved in 1 min or the time for 15% dissolution and the maximum excretion rate.

Effect of food on nitrofurantoin absorption

The effect of food on the absorption characteristics of nitrofurantoin from a commercial capsule dosage form containing macrocrystalline drug and a commercial tablet dosage form containing microcrystalline drug was assessed in human subiects by a urinary excretion method. In fasting subjects, less nitrofurantoin was absorbed and at a slower rate, and attained lower body levels when the capsule rather than the tablet dosage form was orally administered. When each was administered with food, the absorption of nitrofurantoin was appreciably delayed. Food in the gastrointestinal tract produced an increase in the peak body levels of nitrofurantoin from the macrocrystalline form. No effect of food was observed on the maximum levels after the microcrystalline form. There were increases of 80% and 30% in the bioavailability of nitrofurantoin in nonfasting as compared to fasting subiects, of macro crystalline nitrofurantoin capsules and microcrystalline nitrofurantoin tablets, respectively. There was an increase in the duration of therapeutic urinary concentrations of nitrofurantoin when either form was taken with food. The comman practice of using fasting subiects in bioavailability studies of drug products normally administered with food is questionable.

In Vitro Availability of Nitrofurantoin from Different Tablet Batches

AbstractFour commercially available tablet preparations containing 50 mg, and on the other hand, 100 mg nitrofurantoin as well as a test preparation containing 4–5 mg nitrofurantoin was studied in vitro. The tested products meet TISP. XIX specifiactions for drug content and weight. Statistically siginificant differences were recorded between the different preparations with regard to their in vitro availability. Two of the commercial preparations and the test preparation did not meet the USE dissolution requirements for nitrofurantoin tablets.