scholarly journals In Vitro and In Vivo Evaluation of Two Hydroxychloroquine Tablet Formulations: HPLC Assay Development

2020 ◽  
Vol 59 (1) ◽  
pp. 71-78
Author(s):  
Jaber Emami ◽  
Moloud Kazemi ◽  
Anahita Salehi
Keyword(s):  
High Performance ◽  
Internal Standard ◽  
Reversed Phase ◽  
Hplc Method ◽  
In Vivo Studies ◽  
Crossover Fashion ◽  
Content Uniformity ◽  
In Vivo Evaluation

Abstract The relative in vitro and in vivo evaluation of two hydroxychloroquine (HCQ) products was conducted. In vitro studies involved assay, content uniformity and dissolution test, and a two-way crossover fashion were used for in vivo studies. Blood samples were collected at appropriate intervals and HCQ levels were measured using a validated reversed-phase high-performance liquid chromatography (HPLC) method. The drug and the internal standard, chloroquine (CQ), were extracted from blood with diethyl ether, separated and dried under nitrogen gas. Residues were reconstituted in the mobile phase and analyzed at 340 nm on a μ-bondapack C18 (250 × 4.6 mm) HPLC column with acetonitrile:methanol:KH2PO4 (10:10:80) mixture containing 0.01% triethylamine. The standard curve was linear within 50–1,500 ng/mL HCQ (R2 = 0.9996), relative errors were 1.6 to 5%, and the CV% ranged from 7 to 15.4. The resolution factor and RSD were 1.62 and 0.35% and in vitro data of both products met the USP requirements. The 90% confidence intervals for the ratios of the AUC0–96, Cmax and Tmax and their corresponding logarithmically transformed values of generic product over those of Plaquenil® were within the acceptable limit of 0.80–1.20 and 0.80–1.25, respectively. Therefore, the generic HCQ was bioequivalent to the innovator formulation.

scholarly journals High Performance Liquid Chromatoqraphic Method for the Simultaneous Determination of Labetalol and Hydrochlorothiazide in Tablets and Spiked Human Plasma

2004 ◽  
Vol 72 (2) ◽  
pp. 143-155 ◽  
Author(s):  
M. Sultan ◽  
H. Abdine ◽  
N. Zoman ◽  
F. Belal
Keyword(s):  
Simultaneous Determination ◽  
Human Plasma ◽  
High Performance ◽  
Internal Standard ◽  
Reversed Phase ◽  
Hplc Method ◽  
Spiked Human Plasma ◽  
Quantitation Limit

A reversed-phase HPLC method with spectrophotometric detection was developed for the simultaneous determination of labetalol (LBT) and hydrochloro-thiazide (HCD). The chromatographic separation was performed using a Microbondapak C18 column (4.6 i.d. x 250 nm) and paracetamol as internal standard. A mobile phase consisting of 0.05 M phosphate buffer/acetonitrile of pH 4 (7:3) at a flow rate of 0.7 ml/min was used. The detection was affected spectrophotornetrically at 302 nm. The working concentration range was 0.3–10 µg/ml with detection limits of 0.05 µg/ml for both drugs. The lower quantitation limit was 0.25 µg/ml in the two cases. The method was successfully applied to tablets, the % recoveries were 99.45 ± 0.68 for LBT and 99.79 ± 0.75 for HCD. The method was extended to the in-vitro determination in spiked human plasma. The % recoveries were 91.12 ± 0.33 for LBT and 91.37 ± 0.40 for HCD. The interday and intraday precision and accuracy were evaluated in plasma by calculating the % RSD (n=5) and the % error and were found to be in the ranges of 1.18–4.1% and 0.38–0.36% for both drugs, respectively.

Formulation and In Vivo Evaluation of Mucoadhesive Micro-spheres of Rebamipide, a Mucoprotective Drug for GIT Disorders

2018 ◽  
Vol 11 (3) ◽  
pp. 4089-4097
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Amino Acid Derivative ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
In Vitro Drug Release ◽  
Percentage Yield

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  

Biopharmaceutical and Preclinical Studies of Zaleplon as Semisolid Dispersions with Self-emulsifying Lipid Surfactants for Oral Delivery

1970 ◽  
Vol 9 (1) ◽  
pp. 3102-3111
Author(s):  
Narendar Dudhipala ◽  
Arjun Narala ◽  
Dinesh Suram ◽  
Karthik Yadav Janga
Keyword(s):  
Oral Delivery ◽  
Molecular State ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Phase Solubility ◽  
Microscopic Studies ◽  
Pure Drug

The objective of this present study is to develop a semisolid dispersion (SSD) of zaleplon with the aid of self-emulsifying lipid based amphiphilic carriers (TPGS E or Gelucire 44/14) addressing the poor solubility of this drug. A linear relationship between the solubility of drug with respect to increase in the concentration of lipid surfactant in aqueous medium resulting in AL type phase diagram was observed from phase solubility studies. Fusion method was employed to obtain semisolid dispersions (SSD) of zaleplon which showed high content uniformity of drug. The absence of chemical interactions between the pure drug, excipients and formulations were conferred by Fourier transmission infrared spectroscopic examinations. The photographic images from polarized optical microscopic studies revealed the change in crystalline form of drug to amorphous or molecular state. The superior dissolution parameters of zaleplon from SSD over pure crystalline drug interpreted from in vitro dissolution studies envisage the ability of these lipid surfactants as solubility enhancers. Further, the caliber of TPGS E or Gelucire 44/14 in encouraging the GI absorption of drug was evident with the higher human effective permeability coefficient and fraction oral dose of drug absorbed from SSD in situ intestinal permeation study. In conclusion, in vivo studies in Wister rats demonstrated an improvement in the oral bioavailability of zaleplon from SSD over control pure drug suspension suggesting the competence of Gelucire 44/14 and TPGS E as conscientious carriers to augment the dissolution rate limited bioavailability of this active

scholarly journals High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3977
Author(s):  
Shaoyun Wang ◽  
Xiaozhu Sun ◽  
Shuo An ◽  
Fang Sang ◽  
Yunli Zhao ◽  
...  
Keyword(s):  
High Performance ◽  
Chemical Constituents ◽  
Water Extract ◽  
Ethanol Extract ◽  
In Vivo Studies ◽  
Polygonum Multiflorum ◽  
Q Exactive ◽  
Orbitrap Ms

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

Development of an HPLC method for measuring orally administered 1-substituted 2-alkyl-3-hydroxypyrid-4-one iron chelators in biological fluids

1990 ◽  
Vol 36 (1) ◽  
pp. 5-8 ◽  
Author(s):  
J G Goddard ◽  
G J Kontoghiorghes
Keyword(s):  
High Performance ◽  
Biological Fluids ◽  
Internal Standard ◽  
High Performance Liquid Chromatographic ◽  
Reversed Phase ◽  
Hplc Method ◽  
Iron Chelators ◽  
Serum Samples ◽  
Thalassemic Patient ◽  
Serum And Urine

Abstract "High-performance" liquid-chromatographic (HPLC) methods have been developed for identifying 1-substituted 2-alkyl-3-hydroxypyrid-4-one iron chelators in serum and urine. Ion pairing with heptane- or octanesulfonic acid in pH 2.0-2.2 phosphate buffer and reversed-phase chromatography were required to separate these compounds from endogenous compounds in both biological fluids. In both the 2-methyl and 2-ethyl series of 1-substituted compounds (H, methyl, ethyl, or propyl) the elution times increased in accordance with the n-octanol/water partition coefficients (propyl greater than ethyl greater than H greater than methyl). Urine samples were filtered (0.4 microns pore size) and injected either undiluted or after dilution with elution buffer. After the addition of internal standard, the plasma or serum samples were deproteinized by treatment with HCIO4, 0.5 mol/L, centrifuged, and the supernates were injected directly onto the HPLC. Using these procedures, we could identify 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in the serum and urine of a thalassemic patient who had received a 3-g dose of the drug and in the urine of other patients who had received the same dose. One or more possible metabolites were also observed in the chromatograms of both urine and serum. The 24-h urinary output of L1 (0.22-2.37 g) and iron (10.6-71.5 mg) varied but there was no correlation between the two with respect to quantity or concentration. Instead, urinary iron output was higher in patients with a greater number of transfused units of erythrocytes. This is the first study in humans to show that L1 is absorbed from the gut, enters the circulation, and is excreted in the urine.

scholarly journals Melt-Cast Films Significantly Enhance Triamcinolone Acetonide Delivery to the Deeper Ocular Tissues

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 158
Author(s):  
Akshaya Tatke ◽  
Narendar Dudhipala ◽  
Karthik Janga ◽  
Bhavik Soneta ◽  
Bharathi Avula ◽  
...  
Keyword(s):  
Triamcinolone Acetonide ◽  
Polymer Matrix ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Invasive Technique ◽  
Content Uniformity ◽  
Scanning Calorimetry ◽  
Ocular Tissues

Delivering an effective drug load to the posterior section of the ocular tissues, while using a non-invasive technique, has always been a challenge. In this regard, the goal of the present study was to develop sustained release triamcinolone acetonide (TA) loaded polymeric matrix films for ocular delivery. The TA-films were prepared in two different polymer matrices, with drug loadings of 10% and 20% w/w, and they were evaluated for ocular distribution in vivo in a conscious rabbit model. A 4% w/v TA suspension (TA-C) was used as a control for in vitro and in vivo studies. The TA-films, prepared with melt-cast technology, used polyethylene oxide (PEO) and Soluplus® as the polymer matrix. The films were evaluated with respect to assay, content uniformity, excipient interaction, and permeability across isolated rabbit sclera. The distribution of TA in the ocular tissues, post topical administration, was determined in New Zealand male albino rabbits as a function of dose, and was compared against TA-C. The assay of the 10% and 20% w/w film was in the range from 70–79% and 92–94% for the Soluplus® and PEO films, respectively, and content uniformity was in the range of 95–103% for both the films. The assay of the TA from Soluplus® films was less compared with the PEO films and showed an interaction with TA, as revealed by Differential Scanning Calorimetry (DSC). Hence, Soluplus® films were not selected for further studies. No interaction was observed between the drug and PEO polymer matrix. The enhancement of trans-scleral flux and permeability of TA was about 1.16 and 1.33-folds, respectively, from the 10% w/w PEO and 3.5 and 2.12-folds, respectively, from the 20% w/w PEO films, as compared with TA-C formulations. The in vivo studies demonstrate that significantly higher TA levels were observed in the anterior and posterior segments of the eye at the end of 6h with the PEO films. Therefore, the PEO based polymeric films were able to deliver TA into the back of the eye efficiently and for prolonged periods.

scholarly journals DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Release Profile ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Release Mechanism ◽  
In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

scholarly journals FORMULATION, IN VITRO, AND IN VIVO EVALUATION OF TASTE-MASKED ORAL DISINTEGRATING TABLETS OF FEXOFENADINE HYDROCHLORIDE USING SEMISYNTHETIC AND NATURAL SUPERDISINTEGRANTS

2021 ◽  
pp. 99-108
Author(s):  
NAGADANI SWARNALATHA ◽  
VIDYAVATHI MARAVAJHALA
Keyword(s):  
Desirability Function ◽  
Research Work ◽  
In Vivo Studies ◽  
Taste Masking ◽  
Wet Granulation ◽  
Maximum Plasma ◽  
In Vivo Evaluation ◽  
Eudragit Epo

Objective: The aim of the present research work was to prepare and evaluate taste-masked oral disintegrating tablets (ODT) of Fexofenadine hydrochloride. Methods: In the present work, Eudragit EPO, a taste masking agent and Karaya gum (GK) (natural), Sodium starch glycolate, and Croscarmellose sodium (CCS) (semi-synthetic) super disintegrants in three ratios (3, 6,9%) were used. Taste masked granules were prepared by different ratios of the drug: Eudragit EPO (1:1, 1:1.5, 1:2) by wet granulation method. The optimized taste-masked granules (1:2) were selected by sensory evaluation test to prepare 9 Fexofenadine ODT (FH1-FH9) formulations. These were evaluated for different parameters. Then desirability function (DF) was calculated for all formulations using disintegration time (DT), time taken for the tablet to release 90% of the drug (t 90%), and % drug dissolved in 10 min (Q10) as significant parameters. Results: The best formulation (FH6) showed the highest DF value due to less DT and 100% in vitro drug release within 15 min. Thus, FH6 formulation containing 9% CCS was selected as the best among the prepared formulations to which in vivo studies were performed on rabbits to find maximum plasma concentration (Cmax), time taken to reach maximum concentration (tmax), area under the curve (AUC), rate of elimination (Kel), absorption rate (Ka) and half-life(t1/2) and compared with Fexofenadine (Allegra) marketed tablets. Total bioavailability was increased for the test formulation compared to the reference formulation. Conclusion: Fexofenadine was successfully prepared as ODT with increased AUC and decreased tmax to which stability studies were conducted which were found to be stable.

scholarly journals Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Rajni Bala ◽  
Sushil Khanna ◽  
Pravin Pawar
Keyword(s):  
Tensile Strength ◽  
Drug Release ◽  
Content Uniformity ◽  
In Vivo Evaluation ◽  
Disintegration Time ◽  
Significant Difference ◽  
Film Formulation ◽  
Test Film

Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of Cmax (95.87%), tmax (71.42%), AUC0−t (98.125%), and AUC0−∞ (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles.

scholarly journals STABILITY INDICATING RP-HPLC METHOD FOR ESTIMATION OF REPAGLINIDE IN RABBIT PLASMA

2019 ◽  
pp. 206-210
Author(s):  
RAJA NAVAMANISUBRAMANIAN ◽  
SABITHA PANCHAGIRI ◽  
RAGHUNANDAN NERELLA ◽  
CHAMUNDEESWARI DURAIPANDIAN ◽  
SHANMUGANATHAN SEETHARAMAN
Keyword(s):  
High Performance ◽  
Internal Standard ◽  
Cost Effective ◽  
Hplc Method ◽  
Process Efficiency ◽  
Rabbit Plasma ◽  
Long Term Stability ◽  
Rp Hplc ◽  
Resolution Factor

Objective: A simple, selective and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method to estimate repaglinide (REP) in rabbit plasma using rabeprazole (RAB) as an internal standard was developed and validated for various qualifications. Methods: The chromatographic separation was performed on C18 (2) analytical column (5 μ, 250×4.6 mm) using acetonitrile: 0.05% trifluoroacetic acid in water (55:45, v/v) as mobile phase at the flow rate of 1 ml/min. Validation of the analytical method was performed as per ICH guidelines. Results: The retention times of REP and RAB were found at ~4.3 and 5.1 min respectively, with adequate system suitability parameters (theoretical plates ≥3619, tailing factor ≤1.38, resolution factor 2.37). The method has linearity over a concentration range of 10 to 1000 ng/ml (r2=0.9987). The results of accuracy (≥98.17%), intra-, inter-day precision (≤2.9%), recovery (101.21±2.09%) and process efficiency (99.77±3.74%) found satisfactory with no matrix effect. The analyte in samples were found stable up to 6 h, 3 freeze-thaw cycles and not more than 2 mo corresponding to bench-top, short and long term stability studies respectively. Conclusion: The developed RP-HPLC method for estimation of REP in rabbit plasma was developed. The method was found to be rapid, cost-effective and accurate to estimate the REP from the sample matrix. The method can be a most useful tool for in vivo study of REP in the rabbit.

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