In vitro and in vivo study in rats of rectal suppositories containing furosemide (original) (raw)
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ADMET and DMPK, 2020
Furosemide is a diuretic drug widely used in chronic renal failure. The drug has low solubility and permeability, which cause clinical problems. Studying the in vitro release performance elucidates the rate and extent of drug dissolved from dosage forms under different conditions. Furosemide reference tablets were tested using USP Apparatuses 1 and 2 as well as the flow-through cell method (USP Apparatus 4), a dissolution apparatus that simulates the human gastrointestinal tract better than the other methods. Dissolution profiles were created with USP Apparatuses 1 and 2 at 25, 50, and 75 rpm and 900 mL of 0.1 M hydrochloric acid, acetate buffer (pH 4.5), and phosphate buffer (pH 6.8). USP Apparatus 4 with a laminar flow of 16 mL/min and 22.6 mm cells was used. Drug dissolution was quantified at 274 nm for 60 min. Mean dissolution time, dissolution efficiency, time to 50 % dissolution, and time to 80 % dissolution data were used to compare dissolution profiles. Additionally, zero-or...
Journal of Clinical Pharmacology, 2003
F urosemide, a widely used "high-ceiling" loop diuretic drug, is indicated for congestive heart failure, chronic renal failure, and hepatic cirrhosis. 1 Furosemide is absorbed mostly in the stomach and upper small intestine, 2 possibly due to its weak acidic properties (pKa 3.9 3 ), and is characterized by a short half-life of 1.3 ± 0.8 hours (mean ± SD 4 ). The narrow absorption window of furosemide leads to its low bioavailability (49% ± 17%, mean ± SD 5 ).
Effects of surfactant characteristics on drug availability from suppositories
Die Pharmazie, 2008
The addition of surfactants to suppository formulations is referred to in the scientific literature, but their effects on drug availability remain uncertain. Surfactants are reported to improve drug dispersion into hard fatty excipients, to increase the spreading of the melted suppository on the rectal mucosa leading to a greater contact surface, to reduce the viscosity of the molten mass and to reduce the pathway of drug particles to the interface. In the present study a systematic investigation based on tensiometric and rheological methods was carried out to evaluate the effects of nonionic surfactants with different HLBs (hydrophilic-lipophilic-balance) on drug availability and to clarify the possible mechanisms involved in the release process. The relationship between the melted suppositories and a membrane simulating the rectal barrier were investigated in the course of the in vitro release test by measuring their energy characteristics. At the same time, the potential influenc...
Comparison of Generic Furosemide Products by In Vitro Release Studies using USP Apparatus 2 and 4
Dissolution Technologies, 2021
Dissolution studies are essential for comparing the quality of generic drugs to their reference products. The objective of this work was to evaluate the in vitro release of furosemide in tablets under official dissolution conditions and using the flow-through cell method. To this end, two USP apparatus were used: apparatus 2 (paddle at 50 rpm) containing 900 mL of phosphate buffer solution pH 5.8, and apparatus 4 (flow-through cell at 16 mL/min) with the same medium. The dissolved drug was quantified by UV spectrophotometry at 274 nm for 60 min. Although the results at a single time point met the acceptance criterion of Q = 80% at 60 min, the dissolution profiles of generic drugs were not similar to the reference product. The similarity factor (f2 < 50), mean dissolution time, dissolution efficiency, t50%, t80%, and Td values corroborate the difference between the profiles (p < 0.05). In vitro release testing demonstrates that, for furosemide tablets available in Mexico, the g...
Biopharmaceutics & Drug Disposition, 1988
Furosemide tablets, with markedly different dissolution characteristics, and solution were orally administered to 21 healthy adult males to determine the effect of in vitro dissolution rate on in vivo bioavailability profiles. Furosemide 40 mg was given as Tablet A (fast dissolution characteristics), Tablet B (slow dissolution characteristics), and an aqueous solution. Both batches of tablets had identical formulae and were produced by a common process. The dissolution rate of the slower Tablet B was probably retarded by extension of the wet granulation time. Blood was collected for 12 h postdose and urine for 24 h. Peak plasma furosemide concentrations after the solution were significantly greater than after the tablets; there was no significant difference between the tablets. The time to peak occurred significantly earlier with the solution, with no significant difference between the tablets. Relative bioavailabilities of Tablet A and B were 89 per cent and 101 per cent, respectively, as determined by AUC, and 79 per cent and 84 per cent, respectively, as determined by urine recovery. These differences are not statistically significant. These results indicate that dissolution rate profiles of furosemide tablets may not be predictive of in vivo bioavailability.
Layered excipient suppositories: The possibility of modulating drug availability
International Journal of Pharmaceutics, 1997
The release rate of a drug dose from suppositories is affected by characteristics of the excipient (melting temperature and rate, viscosity at rectal temperature, hydro-lipophilic characteristics). Release kinetics from excipients commonly available do not always respond to clinical requirements, even after the introduction of auxiliary agents. Release curves which were differentiated and adaptable to therapeutic conditions were obtained by vehicling a drug in suppositories of two superimposed layers of lipophilic excipients with different characteristics and hence with a difference in drug availability. The two distinct excipient layers release the drug from these suppositories contemporaneously but independently. The amount of drug released in the time course is the sum of the single amounts individually released by the two suppository layers. By previously mixing the two excipients, release rate becomes uniform in the suppository body overall and is conditioned only by the assumed characteristics of the mixture. The release mechanism for superimposed layer suppositories is confirmed by the good agreement between experimental and calculated curves. By using a pair of excipients with different characteristics in superimposed layers between which the drug is distributed, it is possible to modulate drug release kinetics by regulating the reciprocal ratio between the two suppository fractions. © 1997 Elsevier Science B.V.
2018
Suppositories are formulated on weight basis on the assumption that the medication replaces a portion of the suppository base as a function of its density. The effects of drug concentration (C) and drug type (D) on the displacement factor (DF) of drugs in suppository bases (B) were investigated. Three drugs: paracetamol (PCM), sulphathiazole (STZ) and zinc oxide (ZNO), and two bases: polyethylene glycol (PEG) and shea butter (SB) modified with beeswax were studied. Densities of the drugs and bases were determined. Blank and medicated suppositories were prepared using fusion method and the quantity of base displaced by the drug determined. The densities of the drugs and their DF with respect to the two bases ranked ZNO >>> STZ > PCM. An optimum concentration for each drug was obtained beyond which the DF of the drug in the bases remained constant. The bulkier the drug, the smaller the concentration required to determine the displacement factor. No significant difference (...
Micro Determination of Some Diuretic Drugs along with its Pharmacological Activity
The development of Diuretic Drugs is used for the increased production of urine. Commonly known as "water pills," these drugs help your kidneys get rid of extra water and salt from your body through your pee. Because you have less total fluid in your blood vessels, like a garden hose that's not turned on all the way, the pressure inside will be lower. This also makes it easier for your heart to pump. On the basis of oxidation pattern and literature available a possible course of reaction for the preparation of Diuretic Drugs such as Diamox (Tab), synomax (Tab), Tebemid (Tab), Frusemene (Tab), Aquazide (Tab), Xenia (Tab), Kratol (Inj), Mannigyl (Inj), Aldactide (Tab) and spilactone (Tab) are discussed. Background: Diuretics refer to substances that cause loss or removal of excess water from the body in the form of urine. The specific medicines that act as diuretics which are generally referred as the "water pills". Vegetables like asparagus,tomatoes and oats etc. are certain natural diuretic. Since the discovery of thiazide diuretic in 1957, which for the first time offered the possibility of efficiently reducing blood pressure. These drugs have represented a fundamental tool for the treatment of hypertension. Moreover, placebo controlled clinical studies have documented clearly the benefit of thiazide diuretics, either given alone or combined with blockers, in reducing cardiovascular morbidity and mortality. Materials and Methods: 1-5mg of the sample were taken in 100mL stoppered conical flask followed by the addition of 5mL AHC (0.1M) reagent, prepared in 0.5N-HNO3. The reaction mixture was Introduction Rajeev Singh Baghel : 114 shaken well and allowed to react for required reaction time at room temperature (25-30ºC). The unconsumed Ce(IV) was titrated against 0.025M FAS solution using two drops fo ferroin indicator (0.001M). A blank experiment was also performed under identical conditions using all the reagents except the sample. The amount of AHC consumed for the sample was calculated with the difference in the titre values of ferrous ammonium sulphate solution for blank and actual experiments. The recovery of the sample was calculated with the amount of AHC consumed for the sample. For every sample percentage error, coefficient of variation and standard deviation were calculated. Results: The development of Diuretic Drugs is used for the increased production of urine. Commonly known as "water pills," these drugs help your kidneys get rid of extra water and salt from your body through your pee. Because you have less total fluid in your blood vessels, like a garden hose that's not turned on all the way, the pressure inside will be lower. This also makes it easier for your heart to pump. On the basis of oxidation pattern and literature available a possible course of reaction for the preparation of Diuretic Drugs such as Diamox (Tab), synomax (Tab), Tebemid (Tab), Frusemene (Tab), Aquazide (Tab), Xenia (Tab), Kratol (Inj), Mannigyl (Inj), Aldactide (Tab) and spilactone (Tab) are discussed. Conclusion:The development of Diuretic Drugs is used for the increased production of urine. Commonly known as "water pills," these drugs help your kidneys get rid of extra water and salt from your body through your pee. Because you have less total fluid in your blood vessels, like a garden hose that's not turned on all the way, the pressure inside will be lower. This also makes it easier for your heart to pump. On the basis of oxidation pattern and literature available a possible course of reaction for the preparation of Diuretic Drugs such as Diamox (Tab), synomax (Tab), Tebemid (Tab), Frusemene (Tab), Aquazide (Tab), Xenia (Tab), Kratol (Inj), Mannigyl (Inj), Aldactide (Tab) and spilactone (Tab) are discussed.
Journal of Pharmacy and Pharmacology, 1999
This review discusses the possibility of whether furosemide acyl glucuronide, a metabolite of furosemide, contributes to the clinical effect of diuresis. First an analytical method (e.g. HPLC) must be available to measure both parent drug and furosemide acyl glucuronide. Then, with correctly treated plasma and urine samples (light protected, pH 5) from volunteers and furosemide-treated patients, the kinetic curves of both furosemide as well as its acyl glucuronide can be measured. The acyl glucuronide is formed in part by the kidney tubules and it is possible that the compound is pharmacologically active through inhibition of the Na+/2Cl-/K+ co-transport system; up to now the mechanism of action has been solely attributed to furosemide. The total body clearance of furosemide occurs by hepatic and renal glucuronidation (50%) and by renal excretion (50%). Enterohepatic cycling of furosemide acyl glucuronide, followed by hydrolysis, results in a second and slow elimination phase with a...