Stability Of Amoxicillin Research Articles

In vitro stability study of 10 beta-lactam antibiotics in human plasma samples.

Beta-lactam antibiotics are reported for some of them to be subject to a rapid degradation in infusion solutions and in human blood samples. However, the current data of stability available in blood samples are limited to a few number of beta-lactam antibiotics, and the methodology of the corresponding studies may be discussed. The objective of the present study is to evaluate the stability of 10 beta-lactam antibiotics in human plasma samples. Stability of amoxicillin, cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, imipenem, meropenem, and piperacillin was evaluated at low and high concentrations at 20°C, 4°C, -20°C, and -80°C for 1, 7, 60, and 90 days, respectively. Amoxicillin, cefepime, meropenem, and piperacillin were the least stable antibiotics. The maximum durations allowing the stability for all the evaluated beta-lactams at both tested concentrations were estimated at 3h, 23 h, 10days, and 35 days at 20°C, 4°C, -20°C, and -80°C, respectively. We recommend to transport antibiotic plasma samples in ice at 4°C and even at -20°C if these samples come from external hospitals. Ideally, plasma samples should be stored at -80°C if possible; if not, the analysis of the samples should be performed as soon as possible in the limit of 10days after a storage at -20°C.

Influence of pH, light and temperature on the stability of Amoxicillin and Triprolidine HCI.

The stability of two drugs Amoxicillin and Triprolidine . HCl was
 studied in aqueous solution . The results show that Amoxicillin was stable in
 PH range (2-8), while it decomposed at pH more than (6) . The same results
 have been shown when the solution temperature was varied between 25-
 100C° , the decomposition occurred at a temperature above 60C° . When
 Amoxicillin exposed to UV light in presence of O, gas , it was unstable , but
 was relatively stable in the absence of O> gas . Triprolidine HCl was stable
 under the same above condition and factors .
 UV- Visible spectrometer was used to follow the spectrum of two drugs.

Stability of Reconstituted Amoxicillin and Potassium Clavulanate Oral Suspensions Marketed in the Democratic Republic of the Congo

Amoxicillin and Clavulanate potassium oral suspensions are one of antibiotics combination mainly available as dry powders for reconstitution. Made of a β-lactam molecule with a β-lactamase inhibitor, this combination existence can be justified by the potency of Clavulanate potassium which protects Amoxicillin against bacteria producing β-lactamases. Once reconstituted, suspension in single dose bag need to be taken by patient on daily basis following the medical prescription and the one in bottle to be taken according to the medical prescription and the remaining part (in the same container) kept refrigerated in order to get the optimal benefit from the drug. This study investigated the stability of Amoxicillin and Clavulanate potassium suspension both in bags (sachets) for single dose per daily-usage and in bottles for multiple dose usage. The last were reconstituted using distilled water and stored in refrigerator and the previous were instantly reconstituted before measurement. The stability evaluation was conducted on three brands (Six samples totally, two per brand including bottle and sachet for each brand) and for duration of seven days using a validated HPLC method. The evaluation was based on the measurement of pH values, color observation of reconstituted suspensions stored under refrigerator during 7 days and the active compounds concentrations determination. After analysis, no change was observed in pH values and a small change of color for multiple dose presentations stored in refrigerator. And the concentrations of suspensions evaluated in day 1 and day 7 showed over 90% up to seventh day under same storage conditions for both of the Amoxicillin and Clavulanate potassium pharmaceutical presentations. As the study aimed to assess the stability of the suspension in single-dose from bag presentation and in multiple-dose from suspension in bottle, we observed that the reconstituted suspension in distilled water of Amoxicillin + Clavulanate potassium stored in refrigerator is stable for seven days of use, independently from their pharmaceutical presentations either for oral suspensions (powders) in bottles or those in bags for single use after reconstitution.

Simple and reliable extraction and a validated high performance liquid chromatographic assay for quantification of amoxicillin from plasma

This study presents the development of an efficient extraction protocol for amoxicillin from plasma with improved solubility and stability using pH control. Solubility and stability of amoxicillin in commonly used extraction solvents were determined using a newly developed stability-indicating high-performance liquid chromatography (HPLC) method. Following this, protein precipitation (PP) mediated sample purification protocol was developed and validated along with the HPLC method for the extracted amoxicillin from rabbit plasma. The protocol was applied in a pharmacokinetic study in rabbits. A five-fold increase in solubility and two-fold increase in stability of amoxicillin was found by addition of acetate buffer (0.1 M, pH 5.0) in acetonitrile. PP mediated extraction protocol containing acetate buffer-acetonitrile (1:18 v/v) resulted in an extraction recovery of >80% for all the samples. The HPLC assay following extraction was found linear (R2 >0.9999) over the range of 0.2–20 µg/mL with a lower limit of quantification of 0.2 µg/mL. The accuracy of the quality control samples was found between 97–115% and the relative standard deviation (RSD) was found to be below 6% for all samples. The samples were stable in the mobile phase (pH 5.0) for 72 h post-extraction. Amoxicillin-spiked plasma samples were found stable for up to three freeze-and-thaw cycles but, nearly 50% samples had degraded following storage for two months at −20 °C. Pharmacokinetic analysis indicated a half-life of amoxicillin of nearly 1 h following intravenous injection in rabbits, which is similar to that in humans. Thus, a simple and repeatable, extraction protocol was developed using pH control for quantification of amoxicillin from plasma based on its physicochemical properties.

Overcoming stability challenges during continuous intravenous administration of high-dose amoxicillin using portable elastomeric pumps.

While treatment of serious infectious diseases may require high-dose amoxicillin, continuous infusion may be limited by lack of knowledge regarding the chemical stability of the drug. Therefore, we have performed a comprehensive study so as to determine the chemical stability of high-dose amoxicillin solutions conducive to safe and effective continuous intravenous administration using portable elastomeric pumps. First, amoxicillin solubility in water was assessed within the range of 25 to 300 mg/mL. Then, amoxicillin solutions were prepared at different concentrations (25, 50, 125, 250 mg/mL) and stored in different conditions (5±2°C, 25±1°C, 30±1°C and 37±1°C) to investigate the influence of concentration and temperature on the chemical stability of amoxicillin. Finally, its stability was assessed under optimized conditions using a fully validated HPLC-UV stability-indicating method. Degradation products of amoxicillin were investigated by accurate mass determination using high-resolution mass spectrometry. Amoxicillin displayed limited water solubility requiring reconstitution at concentrations below or equal to 150 mg/mL. Amoxicillin degradation were time, temperature as well as concentration-dependent, resulting in short-term stability, in particular at high concentrations. Four degradation products of amoxicillin have been identified. Among them, amoxicilloic acid and diketopiperazine amoxicillin are at risk of allergic reaction and may accumulate in the patient. Optimized conditions allowing for continuous infusion of high-dose amoxicillin has been determined: amoxicillin should be reconstituted at 25 mg/mL and stored up to 12 hours at room temperature (22 ± 4°C) or up to 24 hours between 4 and 8°C.

Postreconstitution Stability of Amoxicillin-Clavulanic Acid Suspensions at Tropical Room Temperature.

The storage conditions of reconstituted β-lactam suspensions are of concern, especially in tropical countries. Improper storage conditions after reconstitution lead to administration of a subtherapeutic dose of medication, which in turn leads to treatment failure and antibiotic resistance.

Evaluation of the quality and stability of amoxicillin oral suspension

The laboratory control of diseases frequently receives powders for oral suspension of amoxicillin, with reports of therapeutic ineffectiveness and problems in reconstituting suspensions. The compendial analyzes not shows quality deviations. This fact motivated the study to assess the quality and stability of oral suspensions amoxicillin in the period of use corresponding to the first and seventh days after reconstitution. Six generic drugs were tested along with the referential drug during its intake period, from the first to the seventh day after powder reconstitution for suspension by high performance liquid chromatographic method. The reconstitution of all samples resulted in suspensions with homogeneous aspect. Both pH assay and amoxicillin identification complied with the product’s specification. The amoxicillin rates were determined in the 1 th and 7 th days after the reconstitution of samples through a method for stability detection, developed and validated before. At the 1 th day, a generic drug sample presented 78% of the rate declared, below the lowest-value specification (90%). In the 7 th day, 3 generic drug samples presented rates below 87%, 83% and 68.1% of the declared value, lower than the minimal specification, thus evidencing pharmacotechnical flaws in the product because of its lack of stability. Percent degradation rates of 3.5%, 4.0%, 6.0%, 9.9%, and 15% amoxicillin in 5 of the generic formulations studied are significant. The present study about amoxicillin oral suspension provides information about the stability during the using period, described for manufacturers. Even though the degradation products have not been identified, they can compromise their safe use, meaning potential risks to the users because of possible toxicity and/or therapeutic inefficacy.

Sterility and Radio Stability of Amoxicillin and Cefaclor Antibiotics Sterilized by Gamma Irradiation

Aim: The present investigations aimed at studying the effect of sterilization by gamma irradiation on amoxicillin and cefaclor antibiotics. They have been irradiated in solid dry state and the probable changes in physicochemical and microbiological properties were studied Place and Duration of Study: The study was carried out from 2011 to 2013 in the Drug Radiation Research Department, Egyptian Atomic Energy Authority. Methodology: Amoxicillin and cefaclor compounds in solid states were exposed to γ irradiation in air atmosphere at room temperature, with a dose of 25kGy and afterwards they had been subjected to microbiological and analytical tests checking their sterility and antibacterial activitiy it was tested against different pathogenic bacterial species by measuring MIC using Microdilution technique and microplate reader. Then their chemical stability were evaluated by different techniques. EPR, FTIR, UV analysis, mass spectroscopy, and melting point. Results and conclusion: The results showed that the majority of initial unirradiated compounds had a slight degree contamination with Bacillus, Micrococcus genera, and fungi. By applying γ irradiation at 25kGy it showed sterilization of the tested antibiotics and keeping their antibacterial activity. The EPR analysis results showed formation of free radicals. The other analytical tests (FTIR), (UV) analysis ,mass spectroscopy, and melting point results proved that the antibiotics analyzed are radioresistant and can be sterilized by irradiation with a dose of 25kGy, without any detrimental effect on their properities and antibacterial activity.

Stability Assessment of Extemporaneous Formulation of Amoxicillin for Parenteral Antimicrobial Therapy

Outpatient parenteral antimicrobial therapy (OPAT) is an important clinical tool in the treatment of severe infections away from the hospital setting. The stability of amoxicillin sodium in elastomeric infusion devices has been determined for parenteral antimicrobial therapy in the outpatient setting. Firstly, stability was studied at either ambient room temperature (25°C ±1), or at refrigerated temperature (4°C). The practice followed at Auckland City Hospital, to reduce manufacturing and delivery costs, is to order the infusion devices in batches of seven – therefore patients can have up to seven devices at home. A second set of experiments was therefore conducted where stability was assessed by simulating real life conditions to which the infusion devices are exposed. These include refrigerated storage for up to 6 days, followed by 24 hours at room temperature to mimic the patient administration period. The stability of amoxicillin was found to be improved when stored at 4°C compared to room temperature. However, significant concentration dependent degradation occurred after seven days; 87% degradation at 83.3 mg/mL down to 11.0 ±0.02 mg/mL, and 54% degradation at 25 mg/mL down to 11.5 ±0.01 mg/mL. Despite this, such formulations continue to be used successfully to treat patients with severe infections. The data generated from this study has been discussed alongside current clinical practice and observed patient outcomes.

Preparation and characterization of amoxicillin mucoadhesive microparticles using solution-enhanced dispersion by supercritical CO2

The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microparticles for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. The chitosan/amoxicillin microparticles were successfully prepared in a process of solution-enhanced dispersion by supercritical CO2 (SEDS). The morphological characteristics of the mucoadhesive microparticles were studied under scanning electron microscope. The resulted microparticles with mean sizes ranged from 1.0 and 2.5 µm had good mucoadhesive properties. In vitro and in vivo mucoadhesive tests showed that chitosan/amoxicillin mucoadhesive microparticles adhered more strongly to gastric mucous layer and could retain in gastrointestinal tract for an extended period of time. The X-Ray Powder Diffractometry and Differential Scanning Calorimetry analysis demonstrated that the SEDS process was a typical physical coating process to produce drug-polymer composite microparticles, which is favourable for drugs since there is no changes in chemistry. In vitro release test showed that amoxicillin released faster in pH 1.0 hydrochloric acid (HCl) than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microparticles to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microparticles had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microparticles of amoxicillin might make a contribution to H. pylori complete eradication.

Determination of Amoxicillin Stability in Chicken Meat by Liquid Chromatography–Tandem Mass Spectrometry

An amoxicillin stability study was performed under different pH (1, 3 and 5) and temperature (4 °C, 22 °C, 37 °C and 55 °C) conditions and for incurred samples stored at −20 °C with the goals of better understanding amoxicillin degradation and characterising its main degradation products (amoxicilloic acid and amoxicillin diketopiperazine). The analytical methodology used consisted of a simple extraction using phosphate buffer (pH 8) with sodium chloride followed by a sample clean-up using OASIS® HLB cartridges and a liquid chromatography–tandem mass spectrometric analysis. Amoxicillin was found to be greatly unstable at temperatures above 22 °C for all pH values studied, so it was recommended that biological samples should be frozen at temperatures below −70 °C until analysis of the amoxicillin residues.

Development and validation of a liquid chromatography/tandem mass spectrometry method for quantitative determination of amoxicillin in bovine muscle

A simple, quick and economical liquid chromatographic/tandem mass spectrometry (LC–MS/MS) method for the quantitative determination of amoxicillin in bovine muscle was developed and validated. The sample preparation procedure involved a liquid extraction with water, followed by a protein precipitation step with acetonitrile. The extract was purified by a liquid–liquid partition with dichloromethane and the upper aqueous layer was directly injected into the LC–MS/MS system. Chromatographic separation was achieved on a reversed phase column, using a mixture of acetonitrile, water and 0.005% formic acid in water as mobile phase. Gradient elution was performed at a flow rate of 0.2 mL min −1. Amoxicillin was detected using positive electrospray ionization in selected reaction monitoring (SRM) mode and was quantified using terbutaline as internal standard. The responses for standards prepared in solvent and in matrix were equivalent and additionally the absence of signal suppression was confirmed by the post column infusion technique. Amoxicillin stability in standard solution and in matrix was investigated at different times and storage conditions. Amoxicillin standards prepared in water were stable on storage up to 20 days at −20 °C. Amoxicillin stability in matrix (spiked bovine muscle samples) was assessed up to 15 days at −20 °C. The method was validated according to the parameters requested by European Commission Decision 2002/657/EC in terms of specificity, linearity, trueness, precision, decision limit (CCα) and detection capability (CCβ). All the trueness values fell within a range between 14.5% and 6.3%. Precision values for all levels of concentration tested were lower than the relative limit calculated by the Horwitz equation. The amoxicillin MRL is set at 50 μg kg −1 and the CCα and CCβ of the method were 61.2 μg kg −1 and 72.4 μg kg −1, respectively.

Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P mucoadhesive microspheres for anti-Helicobacter pylori therapy

The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicate that quantity of emulsifying agent, time for stirring, drug-to-polymers ratio and speed of rotation affected the characteristics of microspheres. Microspheres were discrete, spherical, free flowing and showed a good percentage of drug entrapment efficiency. An in vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 32 full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X1) and stirring speed (X2) on dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency, particle size and t80. The best batch exhibited a high drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 µm. A sustained drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microspheres to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication.

Simple, Economical, and Reproducible LC--MS Method for the Determination of Amoxicillin in Human Plasma and its Application to a Pharmacokinetic Study

A simple, economical, and reproducible high-performance liquid chromatography mass spectrometric (MS) method is developed and validated for the determination of amoxicillin in human plasma. The present method has been successfully used to determine bioequivalence between a test and innovator formulation of amoxicillin 500 mg capsules. The method is validated in terms of selectivity, precision/accuracy, recovery, dilution integrity, matrix effect, effect of anti-coagulant, and stability studies. Sample preparation is carried out by solid-phase extraction (HLB Oasis cartridges). The processed sample is chromatographed on Hypersil Gold (4.6 x 50 mm); 3 microm C18 column, using 10mM ammonium formate buffer (pH 5.0) and acetonitrile, (10:90, v/v) as mobile phase. Amoxicillin is detected by MS-MS detection with turbo-ion spray in positive ion mode. The weighed (1/X2) calibration curves were linear over the range of 0.17 to 17.0 microg/mL. The intra day precision is from 1.3% to 8.8% and intra day accuracy is 94.1% to 108.5%. The inter day precision is from 1.8% to 6.2% and inter-day accuracy is 95.1% to 105.9%. Mean recovery of 66.3% is observed for amoxicillin and 71.6% for internal standard (ampicillin). The stability of amoxicillin is studied at -15 degrees C and -50 degrees C using human plasma with different anti-coagulants (citrate, monobasic sodium phosphate, dextrose, and adenine-citrate, monobasic sodium phosphate, dextrose, and adenine and ethylene diamine tetraacetic acid-ethylene diamine tetraacetic acid). No significant degradation is observed for 60 days.

Application and validation of a LC/fluorescence method for the determination of amoxicillin in sheep serum and tissue cage fluid

A LC method with fluorescence detection after pre-column mercury dichloride derivation was developed and validated for the quantitative determination of amoxicillin in sheep blood serum and tissue cage fluid at levels down to 100 and 200 ng/mL, respectively. Spiked blood serum and tissue cage fluid samples were deproteinized, derivatized with mercury dichloride and extracted prior to reversed phase LC analysis with fluorescence spectrophotometric detection at an excitation wavelength of 355 nm and an emission wavelength of 435 nm. Separation was carried out on a C 18 column with a mobile phase consisting of phosphate buffer, octanesulphonate sodium (OCT), and acetronitrile. A regression model using 1/concentration weighting was found the most appropriate for quantification. The intra-day precision for serum was 1.65–8.74% and for tissue cage fluid was 2.48–6.27%. The inter-day precision for serum was 0.39–3.57% and for tissue cage fluid was 0.44–2.54%. The overall precision over 3 days for blood serum using of 108 replicates was 1.70–9.44% and for tissue cage fluid using of 54 replicates was 2.51–6.76%. Studies of amoxicillin stability in blood serum and tissue cage fluid indicated that amoxicillin was stable after 4 weeks storage at −85 °C. The method was successfully applied for the determination of amoxicillin in blood serum and tissue cage fluid samples collected from rams after intravenous administration.

Stomach Specific Anti-Helicobacter Pylori Therapy: Preparation and Evaluation of Amoxicillin-Loaded Chitosan Mucoadhesive Microspheres

The purpose of this research was to formulate and systematically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use of treating gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing chitosan as mucoadhesive polymer were prepared by simple emulsification phase separation technique using glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking, polymer-to-drug ratio, and speed of rotation affected characteristics of microspheres. Microspheres were discrete, spherical, free flowing and also showed high percentage drug entrapment efficiency. In vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to gastric mucous layer and could retain in gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, polymer-to-drug ratio (X(1)), and stirring speed (X(2)) on dependent variables i.e. percentage mucoadhesion, t(80), drug entrapment efficiency, particle size and swelling index. The best batch exhibited a high drug entrapment efficiency of 70 % and a swelling index of 1.39; percentage mucoadhesion after 1 h was 79 %. The drug release was also sustained for more than 12 h. The polymer-to-drug ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied using scanning electron microscopy. In vitro release test showed that amoxicillin released slightly faster in pH 1.0 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin mucoadhesive microspheres and powder, to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make contribution complete eradication of H. pylori.

In vitro and in vivo studies on mucoadhesive microspheres of amoxicillin

Amoxicillin mucoadhesive microspheres (Amo-ad-ms) were prepared using ethylcellulose (Ec) as matrix and carbopol 934P as mucoadhesive polymer for the potential use of treating gastric and duodenal ulcers, which were associated with Helicobacter pylori. The morphological characteristics of the mucoadhesive microspheres were studied under scanning electron microscope. In vitro release test showed that amoxicillin released faster in pH 1.0 hydrochloric acid (HCl) than in pH 7.8 phosphate buffer. Yet, it would be degraded to some extent in a pH 1.0 HCl medium at 37 °C, which indicated that amoxicillin was not stable in an acidic surrounding. It was also found that amoxicillin entrapped within the microspheres could keep stable. In vitro and in vivo mucoadhesive tests showed that Amo-ad-ms adhered more strongly to gastric mucous layer than nonadhesive amoxicillin microspheres (Amo-Ec-ms) did and could retain in gastrointestinal tract for an extended period of time. Amo-ad-ms and amoxicillin powder were orally administered to rats. The amoxicillin concentration in gastric tissue was higher in the Amo-ad-ms group. In vivo H. pylori clearance tests were also carried out by administering, respectively, Amo-ad-ms or amoxicillin powder, to H. pylori infectious BALB/c mice under fed conditions at single or multiple dose(s) in oral administration. The results showed that Amo-ad-ms had a better clearance effect than amoxicillin powder did. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make contribution to H. pylori clearance.

Assay of amoxicillin sustained release from matrix tablets containing different proportions of Carbopol 971P NF

The sustained release of amoxicillin is desired because of its short biological half-life. Particularly to treat Helicobacter pylori infections, the sustained release is desired to be confined to the upper gastrointestinal tract. In vitro dissolution of amoxicillin has been evaluated utilizing a direct UV-absorption method. However, UV-absorption has been reported as not useful to determine amoxicillin in acidic dissolution test medium. To clarify the suitability of the assay method, the stability and dissolution behavior of amoxicillin sustained release tablets was determined by HPLC, iodometric titration and UV-absorption. Stability of amoxicillin studied under dissolution test conditions of pH 1.2, 37 °C and 50 rpm and determined by HPLC and titration showed considerable degradation of amoxicillin. On the other hand, the UV-absorption increased progressively as amoxicillin degradation proceeded. Amoxicillin release curves determined by different analytical methods show different release profiles, which can be corrected for amoxicillin degradation and change in the UV-absorption to produce similar dissolution results. Release curves determined by UV-absorption and obtained from tablets containing 1017 mg amoxicillin trihydrate and Carbopol 971P NF in a range from 180 to 680 mg showed increasing values of the exponent indicative of the release mechanism ( n) and decreasing release constant values ( k) as the matrix polymer content increased. The release constant ( k) and the exponent ( n) were found to be logarithmically related.

CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability.

A combination of proton pump inhibitors and antimicrobials has been applied as an anti-Helicobacter pylori (H. pylori) therapy. Omeprazole, one of the proton pump inhibitors, is metabolized by CYP2C19. which exhibits genetic polymorphism. It was reported previously that the overall anti-H. pylori efficacy can be related to the CYP2C19 genotype. The main aim of the present study was to obtain a rational explanation for the relationship between the overall anti-H. pylori efficacy and the CYP2C19 genotype. Six healthy volunteers were classified as extensive metabolizers and poor metabolizers, according to their CYP2C19 genotypes. Plasma concentrations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole. The stability of amoxicillin, clarithromycin, and metronidazole was examined using buffer solutions with monitored intragastric pH, and their remaining percentage in the intragastric space was simulated. The poor metabolizers, classified by the CYP2C19 genotypes, showed the higher effectiveness in anti-H. pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly the higher stability of antimicrobials in the higher intragastric pH. CYP2C19 genotyping is a very useful method to determine the effective and safe dosage regimen including the selection of the dual and triple therapy in anti-H. pylori therapy.

Study on the rate of decomposition of amoxicillin in solid state using high-performance liquid chromatography

AbstractAmoxicillin sodium salt degradation in solid state relies on a sequential reaction consisting of two pseudo-first-order processes. Amoxicillin trihydrate, now used in pharmaceutical formulations, is significantly more stable than sodium amoxicillin. It degrades according to Prout-Tompkins model. We studied the stability of amoxicillin at temperatures of 37°, 50°, 80°, 90°, 100° y 110° C. HPLC was chosen as the analytical method. Amoxicillin and its decomposition products are separated by reversed-phase (C18) HPLC with gradient elution.