Quantitation of Propranolol Hydrochloride in Pharmaceutical Dosage Forms by High-Performance Liquid Chromatography

Abstract

A high-performance liquid-chromatography method for the quantitation of propranolol hydrochloride in pharmaceutical dosage forms (capsules, injections and tablets) has been developed. The method can also be used for contents uniformity as required by USP-NF. There is no interference from the excipients present and from hydrochlorothiazide which is often mixed with propranolol hydrochloride. The method is accurate, reproducible and precise with a percent relative standard deviation of 0.6 based on 5 readings. A sample decomposed with sodium hydroxide treatment showed about 9% potency and 2 new peaks in the chromatogram.     

Colorimetric Determination of Piroxicam in Capsules

A simple colorimetric procedure to quantify piroxicam in capsules has been developed. The method is based on the reaction between piroxicam and 4-aminoantipyrine producing an orange color which can be measured at 490 nm. The method is accurate and precise with a percent relative standard deviation of 0.8 based on 5 readings. The results compared very well with the results obtained using the HPLC procedure. The extraction of piroxicam from the capsule powder is very simple which requires only 4 minutes, versus a 30 minute mechanical shaking recommended by the USP-NF. The results of the decomposed samples were similar to the results obtained using the HPLC method.     

Environmentally benign novel green pigments: Pr1-xCaxPO4 (x = 0-0.4)

Rare earth based materials have recently attracted considerable attention as potential ecofriendly colourants for low temperature as well as high temperature applications. In the present study, we have synthesized a series of Ca-doped PrPO₄ compounds with the general formula, Pr_1-xCa_xPO₄ (x = 0-0.4 in steps of 0.1) and characterized the compounds by powder X-ray diffraction. All the compositions show a monoclinic monazite structure. The optical properties of the brilliantly coloured pigments [ L (brightness),a* (+ red- green),b* (+ yellow - blue) have been examined. These materials can find application as potential green colourants.     

Examination of Components of Variance for A Production Scale,Low Dose Powder Blend and Resulting Tablets

Abstract

A study was performed to quantify the contributions of the different components comprising the total variance term observed following the analysis of content uniformity testing of powder blends and tablets. A full scale (400 kg) blend study was performed on a low dose tablet formulation (drug content = 0.13%). Content uniformity samples were pulled from throughout the blender using a pocket type probe thief in a manner which allowed the blend to be assessed for both homogeneity and sample to sample variability at a given location. Tablets were compressed from the batch and assayed for content uniformity. Sampling error accounted for approximately 75% of the variance observed following analysis of drug content in the powder blends. The estimated total variance for the powder blend was approximately twice that observed for tablets compressed from the mixture. The analytical contribution to the total variance term was minor. The difference between the estimated total variance terms for powder blend and tablets was attributed to the superior sampling efficiency of the tablet press versus the sample thief. The results of the study support the use of wider specifications for powder blends than the tablets compressed from the mixture.     

Exact Power Function of Compendial Test Requirements for Content Uniformity

Abstract

The exact distributions associated with the current compendial test requirements are generated by resorting to the well known Computer Intensive Algorithm method to establish the exact percentage point (limit) for RSD, corresponding to each selected cut-off probability level (confidence level) for each of the four possible experimental outcomes based on the USP-NF test requirements. A table is constructed to present the two-dimensional power function. The similarities between these tabular values and the current compendial RSD limits for 10 and 30 dosage units are extremely remarkable.

Minor differences exist, however. It is suggested that both the theoretical as well as the numerical approaches should be carried out to arrive at a comprehensive solution.     

1H-NMR Spectroscopic Assay Method for Metoclopramide Hydrochloride in Tablets and Injections

Abstract

A simple, accurate and specific proton nuclear magnetic resonance (¹H-NMR) spectroscopic method has been developed for the assay of metoclopramide hydrochloride in tablets and injections. In deuterium oxide, the analyte and acetamide, the internal standard, produced corresponding resonance signals at 1.35 ppm and 2.03 ppm of utility for quantitative purposes. The average ± SD recovery of drug from 10 synthetic formulations was 99.7 ± 0.7% of the added amount. The assay of commercial products by the proposed method resulted in average assay values of 100.43 (range = 98.8-100.8, n = 6)% of declared for tablets, and of 99.45 (range = 99.6-100.4, n = 4)% of declared for injections. These results were validated by a high performance liquid chromatographic (HPLC) method.     

Validation of Methods for the Assay of Flurbiprofen and Flurbiprofen Sodium,Related Compounds and Volatile Impurities in Raw Materials and Tablets

Abstract

A high performance liquid chromatographic method has been developed for the assay of flurbiprofen, or flurbiprofen sodium and related compounds in drug raw materials and tablets. A phenyl column with a mobile phase of acetonitrile: 1.0% acetic acid (60:40) provide for the resolution of twenty-one related compounds from the drug. Minimum detectable levels of the related compounds are 0.01% and minimum quantifiable levels are 0.1% or less. Total impurity levels in seven raw materials ranged from 0.0 to 0.6%. One impurity, 2-(4-biphenylyl) propionic acid, is present in most samples at about 0.3%. A gas chromatographic method was developed for organic volatile impurities     

Mucoadhesive tablets for the vaginal delivery of progesterone: in vitro evaluation and pharmacokinetics/pharmacodynamics in female rabbits

Objective: To develop mucoadhesive tablets for the vaginal delivery of progesterone (P4) to overcome its low oral bioavailability resulting from drug hydrophobicity and extensive hepatic metabolism.

Methods: The tablets were prepared using mixtures of P4/Pluronic^® F-127 solid dispersion and different mucoadhesive polymers. The tablets physical properties, swelling index, mucoadhesion and drug release kinetics were evaluated. P4 pharmacokinetic and pharmacodynamic properties were evaluated in female rabbits and compared with vaginal micronized P4 tablets and intramuscular (IM) P4 injection, respectively.

Results: The tablets had satisfactory physical properties and their swelling, in vitro mucoadhesion force and ex vivo mucoadhesion time were dependent on tablet composition. Highest swelling index and mucoadhesion time were detected for tablets containing 20% chitosan-10% alginate mixture. Most tablets exhibited burst release (～25%) during the first 2?h but sustained the drug release for ～48?h. In vivo study showed that chitosan-alginate mucoadhesive tablets had ～2-fold higher P4 mean residence time (MRT) in the blood and 5-fold higher bioavailability compared with oral P4. Further, same tablets showed 2-fold higher myometrium thickness in rabbit uterus compared with IM P4 injection.

Conclusion: These results confirm the potential of these mucoadhesive vaginal tablets to enhance P4 efficacy and avoid the side effects associated with IM injection.     

Quantitation of Ranitidine Hydrochloride in Tablets and Injections Using High-Performance Liquid Chromatography

Abstract

A stability-indicating reverse-phase high-performance liquid chromatography method without the use of a counterion has been developed to quantify ranitidine hydrochloride in pharmaceutical dosage forms. The method is accurate and precise with a percent relative standard deviation of 1.5 based on 5 injections. The extraction procedure for ranitidine from tablets is very simple and there was no interference from the excipients present. Ranitidine appears to be stable to heat on the acidic side and very susceptible to decomposition on the basic side. It lost 84.4% of potency on 20 minute boiling with sodium hydroxide with a new peak in the chromatogram. It lost 37.8% of the potency on treatment with hydrogen peroxide solution for 20 minutes at room temperature with 2 new peaks in the chromatogram.     

Development and Validation of a High-Performance Liquid Chromatographic Method for the Analysis of Propylthiouracil in Pharmaceuticals

A simple, rapid, and stability-indicating high-performance liquid chromatographic (HPLC) method was developed and validated for the assay of propylthiouracil (PTU). The method was used to quantify PTU in topical formulations and in tablets. Excellent linearity was observed between PTU concentration and the peak area (R² = 0.999). The limit of detection was 1 ng, and the limit of quantitation was 1.2 ng. The method proved to be selective. Selectivity was validated by subjecting a stock solution of PTU to acidic, basic, and oxidative degradations. The peaks of the degradation products did not interfere with the peak of PTU. Excipients present in the dosage forms did not interfere with the analysis, and the recovery of PTU from each dosage form was quantitative.     

Quantitative Estimation and Separation of Doxycycline Hc1 and its Related Products

Abstract

An HPLC method is presented for the separation of doxycycline HC1 from its analogs. The method, employing on line U.V. detection allows separation and quantitative estimation of doxycycline HC1 when its analogs are present upto 1% w/w. By this method doxycycline HC1 powder and tablets were analysed     

Aqueous slip casting of MgAl2O4 spinel powder

A stoichiometric MgAl ₂ O ₄ spinel (MAS) powder was synthesized by calcining a compacted mixture of a\boldsymbol{\alpha} -Al ₂ O ₃ and calcined caustic MgO at 1400°C for 1 h and was surface treated against hydrolysis using an ethanol solution of H ₃ PO ₄ and Al(H ₂ PO ₄ ) ₃ after fine grinding. Aqueous suspensions with 41–45 vol.% treated powder were prepared using tetra methyl ammonium hydroxide (TMAH) and an ammonium salt of polyacrylic acid (Duramax D-3005) as dispersing agents. These stable suspensions were consolidated in plaster moulds by slip casting (SC) route for the first time. For comparison purposes, the treated powder was also compacted by die-pressing technique after converting into freeze-dried granules and sintered along with slip cast samples at 1550–1650°C for 1–2 h. The MAS ceramics fabricated by slip casting and die-pressing exhibited comparable properties.     

Preparation,Characterization, and Scale-up of Ketoconazole with Enhanced Dissolution and Bioavailability

ABSTRACT

Many new molecular entities targeted for pharmaceutical applications face serious development challenges because of poor water solubility. Although particle engineering technologies such as controlled precipitation have been shown to enhance aqueous dissolution and bioavailability of poorly water soluble active pharmaceutical ingredients, the data available are the results of laboratory-scale experiments. These technologies must be evaluated at larger scale to ensure that the property enhancement is scalable and that the modified drugs can be processed on conventional equipment.

In experiments using ketoconazole as the model drug, the controlled precipitation process was shown to produce kg-scale modified drug powder with enhanced dissolution comparable to that of lab-scale powder. Ketoconazole was demonstrated to be stable throughout the controlled precipitation process, with a residual methanol level below the ICH limit. The modified crystalline powder can be formulated, and then compressed using conventional high-speed tableting equipment, and the resulting tablets showed bioavailability more than double that of commercial tablets. When appropriately protected from moisture, both the modified powder and tablets prepared from the modified powder showed no change in dissolution performance for at least 6 months following storage at accelerated conditions and for at least 18 months following storage at room temperature.     

Gas Chromatographic Determination of Isbufylline in Tablets for Stability Purposes

Abstract

Isbufylline is a new antibronchospastic drug. A rapid and simple gas chromatographic assay of Isbufylline in tablet matrices has been developed for stability purposes. Isbufylline was extracted from tablets with ethanol containing (l,3-dimethyl-7-amil xanthine) (1 mg/ml) as the internal standard. A filtered aliquot was chromatographed with a 2% OV-17 steel column and the components were detected by a flame ionization detector. The method exhibited good linearity over the range 0.5–1.5 mg/ml (r=0.9997). Mean recovery of isbufylline added to tablet excipients was 99.07%. Mean assay results for 10 and 80 mg tablets were 95.72% and 96.73%, respectively. No degradation was detected during accelerated stability studies at elevated temperatures, confirming the excellent stability of this drug in tablets.     

金属—PAN—S配合物的极谱研究——Ⅱ:Fe~(3+)—PAN—S—TEA—NH_3·H_2O—NH_4Cl体系配合吸附波

在NH_3·H_2O—NH_4Cl—三乙醇胺底液中Fe(Ⅲ)与PAN—S产生一灵敏的配合吸附波,峰电位在—0.50伏(vs.SCE)。峰电位与铁离子浓度在2.8×10~8～3.4×10~(-6)mol/L范围内线性良好,检出下限可达2.8×10~(-8)mol/L。该法用于乳粉、头发、血清等样品的测定,结果满意。     

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson’s disease.

Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.

Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6?h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.

Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson’s disease.     

Effect of moisture content,temperature and exposure time on the physical stability of chitosan powder and tablets

Context: Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations. Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration.

Objective: The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time.

Methods: Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon® VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature.

Results and discussion: The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions. It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets. It was evident that the presence of Kollidon® VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets. The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions.

Conclusion: It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25?°C as well as at a relatively low humidity (<60%) to prevent deterioration of physical properties. Direct compression of chitosan granules which contained 5%w/w Kollidon® VA64 produced the best formulation in terms of physical stability at the different conditions.     

Effect of Tableting Pressure and Geometrical Factor of Tablet on Dehydration Kinetics of Theophyline Monohydrate Tablets

Abstract

The effect of compression pressure and geometrical factors (thickness and diameter) of tablet on the dehydration kinetics of theophylline monohydrate tablets was studied using an infrared water-content measuring instrument. The dehydration rate of 2 cm diameter tablets decreased with increase in tabletting pressure. The dehydration rates of tablets also depended on tablet shape. The 2 cm diameter tablets (thin tablets) dehydrated faster than 1 cm diameter tablets (thick tablets). Dehydration of the powder bed (loosely packed tablets) and 2 cm tablets compressed at 49 MPa followed the two-dimensional phase boundary equation, and that of 2 cm diameter tablets compressed at 98 MPa and 196 MPa (thin tablets) followed the three-dimensional phase boundary equation. Dehydration of 1 cm diameter tablets compressed at 98 MPa (thick tablets) followed the one-dimensional diffusion equation. It seems that the dehydration of the tablet was controlled by the porosity and the surface area of the tablet. Therefore, tablet thickness and tabletting pressure are important factors affecting the dehydration mechanism.     

Second-harmonic generation of a novel transparent material: N,N-diphenyl-8-[2-(4-pyridinyl)ethenyl]-dibenzofuran-2-ylamine

N,N-diphenyl-8-[2-(4-pyridinyl)ethenyl]-dibenzofuran-2-ylamine has been synthesized as a novel second-harmonic generation (SHG) material. From reflection measurement in powder form, the SHG of the titled compound is found to be nine times as intense as that of urea. An effective d coefficient by means of second-harmonic wave generated with the evanescent wave (SHEW) method is estimated to be 3 pm/V. The cutoff wavelength of the compound is 370 nm.     

An Investigation of Some Limitations of the Simple Kinetic Model for Defining Drug Transport in Liquid Membranes

Abstract

The effect of compression (30-150 kp/cm²) and diluent (PVP, lactose) on the in vitro release of PASNa from matrix tablets of mastix was evaluated on the basis of different mathematical models. The Higuchi and the exponential model were proved to be the best statistically. It seems that the use of lactose causes an increase on drug release. Also the relationship between the compression and the packing fraction of the tablets was examined. There seems to be a limit point above which no changes in packing fraction occure.