Pharmacopeia Limits Research Articles

FORMULATION AND CHARACTERIZATION OF SUSTAINED RELEASE TABLET USING MARDI GUM

Objective: The present research work was to develop and evaluate alprazolam sustained release tablet using Mardi gum, a comparative study on binding properties of gum and hydroxypropyl methylcellulose (HPMC) was performed.
 Methods: Formulation of alprazolam tablets (f1–f6) was done by direct compression method using 15%, 30%, and 45% concentration of gum as a natural binder, and HPMC was used as synthetic matrix forming agent. Microcrystalline cellulose was used as diluents, talc, and magnesium stearate as a lubricant and PVP K30 as the binder. The formulated batches were evaluated for parameters such as tablet thickness, % friability, hardness, weight variation, and in vitro drug release characteristics. The release information was fitted into different dynamics models to decide the release mechanism of the drug.
 Results: The results showed that all the parameters of the developed tablets (f1–f6) were in fulfillment with pharmacopeia limits. In vitro, drug release studies showed that formulation f1 had most controlled and sustained manner releaser with maximum drug release of 97.89±0.52% in 18 h with comparison to f2–f4 and f6 drug release is 98.12±0.55%, 97.24±0.57%, 98.16±0.74%, and 97.26±0.35%, respectively, in 16 h and f5 giving 97.89±0.85% release in 14 h.
 Conclusion: On the basis of obtained result, it can be concluded that Mardi gum can be used to sustain the drug release as a natural polymer in tablet dosage form.

Comparative Quality Control Study of Different Brands of Diclofenac Sodium Tablet Available in Local and Government Pharmacies by In-Vitro Testing.

The objective of this study is to conduct in-vitro quality control testing of diclofenac sodium tablets involves weight variation test, drug assay, friability test, and the disintegration and dissolution test. Two brands of diclofenac sodium tablets were used in the study, named Brand A and Brand B. Quality control (QC) test results for diclofenac sodium tablets show that both Brand A and Brand B conform to the United States Pharmacopeia (USP) standards. In terms of weight variation, Brand A and B have an above the mean weight limit variation of 2.79% and 2.05%, respectively. The lower mean weight limit variations are 1.21% and 1.27%, respectively, which are within the 10% standard limits of USP. Friability tests show that Brands A and B have an average friability of 0.062% and 0.01% mass loss, which are within the 1% mass loss limits of USP. In terms of drug assay, both Brands A and B fall under the USP parameter of 85%-115%, respectively. The disintegration test shows that Brand A and Brand B fall within a 15-minute time interval segment with disintegration time calculated as 6.69 min and 7.02 min for Brands A and B, respectively. Brand B of Diclofenac Sodium has a drug dissolution percentage of 90.7% within a 45-min sampling time interval.Brands A and B pass the pharmacopeia limits set under the USP standards. The friability test shows that the loss of mass for both Brands A and B was within the 1% standard limit. Similarly, with regard to weight variation, both brands conform under the normal limit of 10% above or lower the mean weight. In terms of drug assay, both brands' drug availability was within the specified 85%-115% standard range. They passed the disintegration and dissolution test within a time limit of less than 15 minutes and 45 minutes, respectively.

Formulation and Evaluation of Extended Release Matrix Tablets of Tenatoprazole Sodium using Synthetic Polymers

Extended release formulations are designed to release their medication in a controlled manner at a predetermined rate, duration and location to achieve and maintain optimum therapeutic blood levels of a drug. The present investigation is aimed to formulate the extended release matrix tablets of Tenatoprazole sodium with various grades of different polymers like Carbopol, HPMC and Eudragit grades. The tablets were prepared by wet granulation technique. The prepared ER Matrix tablets were evaluated for various physico chemical parameters. All the formulations resulted in acceptable Pharmacopoeia limits. In-vitro drug release studies (USP dissolution rate test apparatus II, 75 rpm, 37°C ±0.5°C) using 0.1N hydrochloric acid (1.2 PH ) for first 2 hrs and phosphate buffer (PH 6.8) as a dissolution medium (900ml) for the next 12 hrs. Among all the formulation F-5(drug: Carbopol-974P-NF in ratio of 1:1.5) shows better result upto 12 hours of the drug release was found to be 99.47±0.22 so it’s an Optimized formulation. Key words: Carbopol, ER Matrix, Eudragit, Methocel, Tenatoprazole sodium, Wet granulation.

Detection and risk assessments of multi-pesticides in 1771 cultivated herbal medicines by LC/MS-MS and GC/MS-MS

Focus on the safety of herbal medicines has mainly been directed towards the presence of intrinsic toxicity, as found in the cases of renal and hepatic dysfunction caused by aristolochic acids. However, contamination from extrinsic hazards may impart an even greater reduction in their safety and efficacy. This study reveals that pesticides were present in the majority (88%) of a comprehensive cross-section (n = 1771) of herbal medicine samples. Alarmingly, more than half (59%) contained pesticides over the European Pharmacopoeia (EP) limit, and 43% of them contained 35 varieties of banned, extremely toxic pesticides, eight of which were detected at levels over 500 times higher than the default Maximum Residue Limit (MRL). DDTs, carbofuran, and mevinphos were confirmed as being among the most risk-inducing pesticides by three different risk assessment methods, reported to produce carcinogenic, genotoxic, reproductive, and developmental effects, in addition to carrying nephrotoxicity and hepatotoxicity. In light of these findings, and withstanding that extrinsic hazards can be controlled unlike intrinsic toxicity, the authors here strongly recommend the application of herbal medicine quality-control measures and solutions to safeguard against a neglected but certainly potentially serious health risk posed to the majority of the global population that consumes herbal medicines.

The DESIGN AND DEVELOPMENT OF CARVEDILOL GASTRORETENTIVE FLOATING DRUG DELIVERY SYSTEMS USING HYDROPHILIC POLYMERS AND IN VITRO CHARACTERIZATION

Objective: The primary aim of the present examination was to create carvedilol phosphate floating tablets using factorial designs and for retention in the upper portion of the gastrointestinal (GI) tract to sustain the dissolution where the solubility of carvedilol phosphate is more in an acidic medium.
 Methods: The floating tablets of carvedilol phosphate were ready to employ different concentrations and a combination of these polymers of Na-alginate, Carbopol 934P, and sodium carboxymethyl cellulose (NaCMC) with lubricants magnesium stearate by direct compression technique. In the present experiment, involved sodium bicarbonate and citric acid as a gas-producing agent. Fifteen formulations structured and judged for pre-compression components like the angle of repose, bulk and tapped density, Hausner’s ratio, compressibility index, and post-compression factors are weight uniformity, hardness, drug content, friability, in vitro buoyancy, dissolution studies, and Fourier transforms infrared spectroscopy (FTIR).
 Results: The drug released 90.02% in 12 h by combining NaCMC (7.5 mg) and Na-alginate (7.5 mg) in the formulation F14 towards the achievement of sustained release. Batch F14 selected as optimized, as provided desired zero-order release profile as well as floating lag time 20 s and total floating time>12 h, and the mechanism of drug release observed (n = 1.098, super case-II transport).
 Conclusion: From the results fulfilled that all the preparation found to be within the pharmacopeia limits and was the best dosage form to treat moderate heart failure and hypertension. The in vitro dissolution profiles of all formulations placed into various kinetic models, the statistical parameters like slope, regression coefficient and intercept determined. The gastro-retentive dosage form to maintain the sustain drug delivery, which would improve the maximum therapeutic efficacy and patient compliance.

Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats

A novel pure insulin spray-dried powder for DPI product (Ins_SD) was studied with respect to physico-chemical stability, in vitro respirability, bioavailability, activity and tolerability.Ins_SD powder exhibited a very high in vitro respirability, independently of the DPI product preparation (manual or semi-automatic). Physico-chemical characteristics of Ins_SD powder remained within the pharmacopoeia limits during 6 months of storage at room temperature.PK/PD profiles were measured in rats that received the pulmonary powders by intratracheal insufflation and compared with Afrezza inhalation insulin. Due to the low drug powder mass to deliver, both insulin powders were diluted with mannitol. Insulin from Ins_SD was promptly absorbed (tmax 15 min and Cmaxx4.9 ± 1.5 mU/ml). Afrezza had a slower absorption (tmax 30 min and Cmax of 1.8 ± 0.37 mU/ml). After glucose injection, Ins_SD determined a rapid reduction of glucose level, similar to Afrezza. As reference, insulin subcutaneous injection showed a long-lasting hypoglycemic effect due to the slow absorption that prolonged insulin plasma level.In summary, Ins_SD product is suitable for post-prandial glucose control, providing a convenient and compliant product, in particular in the event of using a disposable device.Albeit the product has to be stored in fridge, its stability at room temperature allows the diabetic individual to carry the daily dose in normal conditions.

A A COMPARATIVE STUDY OF QUALITY CONTROL TESTING ON CANDESARTAN CILEXETIL CONVENTIONAL TABLETS IN IRAQ

Objective: The present study was performed to compare the quality of conventional tablets loaded with candesartan cilexetil. The selected candesartan cilexetil tablets were commercialized in the Iraq market and produced by different companies. 
 Methods: Different batches of candesartan cilexetil oral tablets (the concentration of candesartan was 8 mg) were subjected to quality control tests. Tests included weight variation, friability, hardness, drug content, disintegration time and in vitro release study. The protocols of these tests were performed according to USP pharmacopeia.
 Results: The results, in this study, revealed that all the used batches of candesartan cilexetil oral tablets complied with the specification of USP pharmacopeia for weight uniformity, friability value (% loss) was<1. Hardness results of the tablets were 4.9-6.6 Kg/cm2, which was within the required limits (i.e. 4-8 Kg/cm2). Disintegration time was<15 min in both Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF). The percentage of drug content in all marketed tablets was found between 96.2 % and 99.8 %, reflecting compliance with the pharmacopeia limits (i.e. 85-115 %). An in vitro release study indicated that the release of all marketed tablets exceeds 80 % within 15 min.
 Conclusion: All the studied tablets, loaded with candesartan cilexetil, were produced within the standard criteria of tablet production. The quality control analysis of the selected tablets, in this study, revealed satisfactory pharmaceutical properties (including safety and effectiveness) that comply within the limits of USP pharmacopeia.

Formulation and Evaluation of Colon Targeted Enteric Coated Tablets of Loperamide

In this study the formulation of safe and effective enteric coated matrix tablet of Loperamide was prepared for the effectual treatment of inflammatory bowel diseases. Direct compression method is used for the formulation of colon targeted matrix tablet of Loperamide. Eudragit FS 30 D polymer and Triethyl citrate this coating material is used for this tablet. This coated tablet evaluated for properties such as average weight, hardness and coat thickness. The In vitro release studies of prepared tablets was carried out for 100 rpm for first 2 hrs. Then replaced with 7.4 pH phosphate buffer and continued for 24 hrs. According to United States Pharmacopoeia (USP) limits, the percentage weight variation, percent friability and content of drug molecule for all the formulations are in the range of USP limits. From the results obtained, Loperamide would be a hopeful formulation to achieve the aim which cure inflammatory bowel diseases without any gastric irritation, which is helpful for patients having pre-history of ulcerative colitis.

Automated fluorimetric determination of the genotoxic impurity hydrazine in allopurinol pharmaceuticals using zone fluidics and on-line solid phase extraction

In the present study we report a fully automated method for the determination of low levels of the genotoxic impurity hydrazine in allopurinol active pharmaceutical ingredient (API) and formulations based on the concept of zone-fluidics. Hydrazine reacts on-line with o-phthalaldehyde in a unique way, that is in acidic medium (pH < 1.5) and in the absence of nucleophilic reagents, to form a highly fluorescent hydrazone (λex/em = 318 / 376 nm). The adaptation of a 120 s long stopped-flow step at elevated temperature (70 °C) offered adequate sensitivity (LOD =0.9 μg L−1 or 0.1 ppm in the solid API) to meet the pharmacopoeia limits for the selected application. The analyte was separated efficiently from the excess of the API by on line solid phase extraction using a Hydrophilic-Lipophilic technology sorbent that provided direct retention of the more hydrophobic API without the need of wetting/conditioning steps. Percent recoveries ranged between 93.3 and 105.8%.

Degradation studies of quetiapine fumarate by liquid chromatography-diode array detection and tandem mass spectrometry methods.

Quetiapine fumarate (QUE) is an antipsychotic agent with a chemical structure that is susceptible to degradation; therefore, it is important to study its stability using appropriate analytical tools. Knowledge of the stability profile of a drug is important because chemical degradation of its active component often results in a loss of potency, affecting its efficacy and safety. This current work reports degradation studies of QUE as drug substance, under different stress conditions such as oxidation, hydrolysis, heat, humidity and photolysis, by a stability-indicating LC method. The chemical stability was evaluated using a simple HPLC/diode array detection method, with a core-shell C18 column under isocratic conditions, which allows the separation of all primary degradation products (DPs) in a short run time. QUE was mainly degraded under oxidative and hydrolytic conditions, with the formation of three and two DPs, respectively, which were identified by electrospray ionization-tandem mass spectrometry. The method was properly validated in terms of linearity, accuracy, precision, selectivity, robustness and quantitation limit. Commercial tablets containing 25 mg of QUE were quantified, with results obtained within the United States Pharmacopeia limits. The proposed method is suitable to assess the stability and perform routine analysis of QUE in pharmaceutical samples.

Microbiological safety of commonly available eye ointments and their in-vitro anti-bacterial potency

Current study attempted to check out the microbiological quality of some common sterile ointment commonly implemented for the treatment of eye infections in Bangladesh. Seventeen (17) different eye ointment (T-Mycin, Aprocin, Bactin, Optimox and Cloram, Hypomer gel, Sonexa, Polytracin, Cero, Aristobet, Lotepred, Herpigel, Gentob, Xoviral, Zirgan, Xovir, Tomycin, Tobirax, AFm-plus and Parafresh) were microbiologically examined through common and traditional cultural methods. Total viable bacterial and fungal contamination was found up to 106 and 105 cfu/ml respectively. Among the 17 samples T-Mycin, Aprocin, Sonexa, Polytracinand Tomycinwere free from fungal contamination. All the samples significantly exceeded United States Pharmacopeia (USP) or British Pharmacopeia (BP) limit (&lt;102 cfu/ml) in case of Total viable bacteria and fungus contamination. While the coliforms (Escherichia coli and Klebsheilla spp.) were absent in all samples, the prevalence of Staphylococcus spp. was 100% in all samples up to 103 while the Bacillus spp. was found up to 102 cfu/ml. Pseudomonas spp. was cultivated in TMycin, Aprocin Hypomer gel, Sonexa, Polytracin, Cero, Aristobet and Lotepred up to 103cfu/ml. All the 5 drugs showed their antibacterial potency with satisfactory range of zone diameter againstE. coli, Pseudomonas spp., Staphylococcus spp., Klebsheilla spp. and Bacillus spp. In case of all 17 ointments the average zone diameter range was noticed within 13mm-22mm. The highest zone diameter (22mm) was recorded against E. coli produced by Aprocin and minimum zone diameter (13mm) was recorded against Bacillus spp. produced by Bactin, Optimox and Cloram.Gentamicin and Streptomycin were used as positive control against the tested bacteria.&#x0D; Bangladesh J Microbiol, Volume 35 Number 2 December 2018, pp 122-126

Fabrication and characterization of fast dissolving films of H2-receptor antagonist

Objective: The aim of the present study was to develop a fast dissolving film (FDF) of taste masked inclusioncomplex of Famotidine (FMT) using film forming polymer. Method: FDFs were prepared by solvent castingmethod. The developed FDFs were characterized for film thickness, disintegration time, flexibility, dissolutionstudy. The developed FDFs of FMT were transparent, elegant, smooth and homogenous. Results: Physicochemicalcharacterization of FDFs showed no interaction between the drug and film forming polymer. The drug content wasfound in the range of 96.05 to 102% and disintegration time was found in pharmacopoeia limit, which was less than1 min. In vitro drug release study showed that approximately 82% drug release within 60 sec. Conclusion: Fast Dissolving film of famotidine is prepared that dissolve within one minute when placed on tongue. It gives fact actionbecause it avoids the first pass metabolism. These films are preferred in geriatric and pediatric patients.

The Mechanical and In vitro Release Properties of Diazepam from Tablets Containing Fluid Bed Dried and Lyophilized Cocos nucifera Microcrystalline Cellulose

Aim: This study aimed to evaluate the mechanical and in vitro release properties of diazepam from tablets containing fluid bed dried and lyophilized microcrystalline cellulose (MCC) obtained from the matured fruit husks of Cocos nucifera (CN).&#x0D; Study Design: Method of experiment.&#x0D; Place and Duration of Study: Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka from March 2015 to September, 2016&#x0D; Methods: Dried CN fruit husks were digested in sodium hydroxide to obtain alpha (α) cellulose which on hydrolysis with mineral acid (Hydrochloric acid) solution gave CN-MCC. The dry MCC obtained by either fluid bed or lyophilized drying of the wet CN-MCC were coded MCCF-Cocos and MCCL-Cocos respectively. Both MCCs were used in the formulation of diazepam tablets at 20, 30 and 40% w/w. Avicel PH 102 (AVC-102), was used as comparing standard. The tablets were evaluated for physical and dissolution properties using standard methods.&#x0D; Results: Results show the tablets passed the British Pharmacopoeia specifications for weight uniformity, crushing strength, disintegration time, friability and dissolution. Diazepam tablets containing MCCL-Cocos (coded DCL) were mechanically stronger than those containing MCCF-Cocos (coded DCF). Disintegration time was in the order of DCF &gt; DCL tablets while friability was in the order of DCL &lt; DCF tablets. Diazepam tablets containing AVC-102 (coded DAV) were mechanically stronger than DCL and DCF tablets. The dilution potential was in the order DAV &gt; DCL &gt; DCF. More than 80% of the diazepam content was released from DAV, DCL and DCF tablets.&#x0D; Conclusion: Generally, DAV, DCL and DCF tablets met the British Pharmacopoeia limits for mechanical properties and in vitro drug release with DCL tablets showing significantly (P = .05) superior mechanical properties while DCF showed faster drug release.

Determination of arsenic speciation in 17 commonly used traditional Chinese herbal medicines by HPLC-ICP-MS

The element speciation analysis for heavy metals in herbal medicines is still in the beginning stage. In this study,the total amount of arsenic( As) in 103 batches of 17 commonly used Chinese medicines( including 16 plant medicines and 1 medicinal fungus) was detected by inductively coupled plasma mass spectrometry( ICP-MS). Furthermore,based on HPLC-ICP-MS,the simultaneous detection methods of six As speciation kinds in traditional Chinese medicines were established. An AS7 anion exchange column was selected and the As forms in 17 traditional Chinese medicines was systematically analyzed. The results showed that the method of pretreatment of medicinal materials by microwave digestion and the detection of total amount of As by ICP-MS was stable and reliable. As for the speciation analysis of As,the high-speed ultrasonic extraction method was adopted,and it showed that the linear relationship of the six As speciation was satisfied with the correlation coefficient R2>0. 999 9. The LOQ of six kinds of As speciation were 0. 20,0. 10,0. 15,0. 10,0. 25,0. 10 μg·L~(-1) for arsenic betaine( As B),arsenious acid [As( Ⅲ) ],dimethyl arsenic( DMA),arsenic choline( As C),monomethyl arsenic( MMA),arsenic acid[As( Ⅴ) ],respectively. The recoveries were between 84. 24% and 121. 5%,and the relative standard deviations were 2. 7% to 11%. Among the 103 batches of medicinal materials,only one batch of sample As exceeded the Chinese Pharmacopoeia limit standard; As( Ⅲ) and As( Ⅴ) had high detection rate in 103 batches of Chinese herbal medicines,within which As( Ⅴ) was the main detected form,and inorganic As accounted for the ratio reached 80. 90%-98. 73%; some samples detected DMA,MMA and As B,As C was not detected in any batch. This study established an analytical method suitable for the speciation of As in Chinese herbal medicines,and provided basic data for As residual residue in Chinese herbal medicines,which can provide important reference for the risk assessment and quality standards.

Stability of commercial parenteral lipid emulsions repacking to polypropylene syringes.

To accommodate small fluid volumes, repackaging of intravenous lipid emulsions is frequently performed in hospitals providing parenteral nutrition to neonates and smaller pediatric patients. The physical stability of lipid commercial parenteral emulsions repacked and stored in polypropylene syringe up to 30 days at room temperature, refrigerator and 40°C was determined to establish options for extended storage. Lipid emulsions in the manufacturers’ original containers were used as references. Commercial lipid emulsions (20% of oil phase), ClinOleic, Intralipid, Smoflipid, Omegaven and Lipofindin LCT/MCT were repackaged under aseptic conditions in polypropylene syringes and stored at 4°C, 25°C and 40°C without light protection. Samples were assayed periodically over 30 days using validated, stability-indicating methods. Lipid emulsions in the manufacturers’ containers stored in the same conditions were as references. Analysis of variance showed differences in the physical parameters due to temperature (p<0.05) and study day (p<0.05) but not the type of the emulsion (p = 0.98). The parenteral lipid emulsions in polypropylene syringe exhibited identical (except Z-avarage at 40°C, t = 30 days) to original containers time-dependent behavior taking into account the mean globule size, pH, and zeta potential measurements. Size of oily droplets of all test conditions remained below the United States Pharmacopeia limits. The results allow safe repacking of commercial lipid emulsion in a syringe, which is a necessary condition for supplying parenteral nutrition using the two-in-one method for newborns. However, longer storage than 12 h of repacked emulsion needs microbiological studies.

Hydrophobic-interaction chromatography for purification of influenza A and B virus

Options for hydrophobic-interaction chromatography (HIC) for purification of cell culture-derived influenza A and B virus have been assessed using a 96-well plate format using a semi-high-throughput approach. Follow-up experiments at preparative scale were used to characterize dynamic binding capacity, viral hemagglutinin protein (HA protein) recovery, and the influence of influenza virus (IV) strains on yield and contamination levels. Virus recoveries of up to 96% with a residual DNA level of about 1.3% were achieved.To achieve DNA contamination levels required for manufacturing of influenza vaccines for human use, a purification train comprising clarification, inactivation, concentration, column-based anion-exchange chromatography (AEC), and HIC was used in a final set-up. AEC using strong quaternary ammonium ligands was applied as an orthogonal method for DNA depletion by adsorption. Subsequently, HIC (with polypropylene glycol as functional group) was used to reversibly bind virus particles for capture and to remove residual contaminating DNA and proteins (flow-through). This two-step chromatographic process, which requires neither a buffer exchange step nor nuclease treatment had a total virus particle yield for IV A/PR/8/34 (H1N1) of 92%. The protein and the DNA contamination level could be reduced to 42% and at least 1.0%, respectively. With 17.2 μg total protein and 2.0 ng DNA per monovalent dose, this purity level complies with the limits of the European Pharmacopeia for cell culture-derived human vaccines. Overall, the presented downstream process represents a valuable alternative to existing virus purification schemes. Furthermore, it utilizes only off-the-shelf materials and is a simple as well as an economic process for production of cell culture-derived viruses and viral vectors.

A simple dilute-and-shoot method for screening and simultaneous quantification of nicotine and alkaloid impurities in electronic cigarette refills (e-liquids) by UHPLC-DAD

The electronic cigarette (e-cigarette) has emerged as a popular alternative to the traditional hazardous tobacco cigarette. The substantial increase in e-cigarette use also urgently calls for controlling the quality of e-cigarette refill liquid products (e-liquids). Currently, the most important quality indicator of e-liquid products is the quantification of nicotine and its related impurities. Although different methods have been published to measure nicotine and impurity levels, the majority of them use a targeted LC-MS/MS approach. There is, however, a need for more robust quantification methods that are easy to implement in most control (industrial and governmental) laboratories. Therefore, in this study, a simple dilute-and-shoot UHPLC-DAD method has been developed and validated for the simultaneous quantification of nicotine and its alkaloid impurities in electronic cigarette refills. An optimal separation of the alkaloids was achieved in a runtime of 11 min. The method was successfully validated using the “total error” approach in accordance with the validation requirements of ISO-17025. During this validation, interference between the target components and a number of popular flavouring compounds such as vanillin, maltol, ethylacetate, etc. could be excluded. In addition, small changes to the column temperature, pH and molar concentration of the mobile phase buffer were deliberately introduced in order to assess the robustness of the method. Only a slightly different outcome between the newly developed UV-detection method and the targeted MS approach was found, due to the sensitivity of the different detection techniques. However, in the context of quality control of nicotine related impurities, for which the European Pharmacopoeia limits are currently applied, the sensitivity of the UHPLC-DAD method was found to be within the acceptable range. Despite the somewhat lower selectivity of the newly developed UV-detection technique versus a targeted LC-MS/MS approach, it may be concluded that this method is a suitable alternative for quality control purposes.

Pesticides in Herbal Medicines, the Insidious Public Health Hazard: Multi-Residue Pesticide Analysis and Risk Assessments Based on 1771 Samples

Background: Focus on the safety of herbal medicines has mainly been directed towards the presence of intrinsic toxicity, as found in the reported cases of renal and hepatic dysfunction caused by aristolochic acids. However, contamination from extrinsic hazards may have the potential to impart an even greater reduction in their safety and efficacy. Methods: Currently available herbal medicine samples from large-scale cultivation areas in major herbal medicines markets in China were collected for analysis of pesticides by LC/MS-MS or GC/MS-MS. Additionally, dietary exposure assessment, risk-ranking score and comparative health impact analysis were employed to estimate the hazard potential of pesticide residue exposure in herbal medicines. Findings: This study reveals that pesticides were present in the majority (88%) of a large, comprehensive cross-section (n=1771) of herbal medicine samples. Alarmingly, more than half (59%) contained pesticides over the European Pharmacopoeia (EP) limit, and 43% contained 35 varieties of banned, extremely toxic pesticides, eight of which were detected at levels over 500 times higher than the default Maximum Residue Limit (MRL). DDTs, carbofuran, and mevinphos were confirmed as being among the most risk-inducing pesticides by three different risk assessments methods, reported to produce carcinogenic, genotoxic, reproductive, and developmental effects, in addition to carrying nephrotoxicity and hepatotoxicity. Interpretation: Herbal medicines are severely contaminated with risk-inducing pesticides, therefore the authors strongly recommend the application of quality-control measures to safeguard public health. Funding Statement: This study was funded by the Study on the Key Safety Validation Elements of Chinese Medicine in International Trade, International Science & Technology Cooperation Program, PR China (2015DFM30030) and the OLCA-Pest Project, financially supported by ADEME, Denmark (17-03-C0025). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Not required.

FORMULATION AND EVALUATION OF COLON TARGETED MATRIX TABLET USING NATURAL TREE GUMS

Objective: To develop a novel colon targeted tablet formulation using natural polysaccharides such as kondagogu gum and ghatti gum as carriers and diltiazem hydrochloride as a model drug.Methods: The polymer-drug tablets were prepared by wet granulation technique, coated with two layers viz., inulin as an inner coat followed by shellac as outer coat and evaluated for properties such as average weight, hardness and coat thickness. In vitro release studies of prepared tablets were carried out for 2 h in pH 1.2 HCl buffer, 3 h in pH 7.4 phosphate buffer and 6 h in simulated colonic fluid (SCF) in order to mimic the conditions from mouth to colon.Results: Percentage weight variation, percent friability and content of active ingredient for all the formulations were found to be well within United States Pharmacopoeia (USP) limits. Out of both the polymers, the tablets prepared with ghatti gum showed the maximum hardness of 7.1 kg/cm2. The FTIR spectra of pure diltiazem HCl and the formulation KF3 were found to be identical. From the DSC, it was evident that the melting point peak of diltiazem HCl and formulation KF3 were observed at 217.16 and 218.34 °C respectively. In vitro studies revealed that the tablets coated with shellac (2.5% w/w), prevented the drug release in stomach environment and inulin coated tablets (4% w/w) have limited the drug release in the small intestinal environment. The data obtained from in vitro drug release studies were fit into Peppas model and in all the cases the value of A was found to be more than 2, i.e., drug release by a combination of both diffusion and erosion-controlled drug release.Conclusion: The study revealed that polysaccharides as carriers and inulin and shellac as a coating material can be used effectively for colon targeting of drugs for treating local as well as systemic disorders.

In-capillary derivatization with fluorescamine for the rapid determination of adamantane drugs by capillary electrophoresis with UV detection.

In-capillary derivatization using fluorescamine as the labeling reagent was proposed to enhance the detectability of adamantine drugs (memantine, amantadine and rimantadine) by spectrophotometric detection. Fluorescamine and the drugs were delivered to the capillary electrophoresis instrument at a ratio of 10:1 by zone injection. The derivatization reaction occurred following the application of voltage (20kV). The derivatized products, hydrolyzed- fluorescamine and excess fluorescamine were separated in 7min using 100mM borate buffer (pH10.0) containing 0.1% w/v of Brij®-35 and 20% v/v of acetonitrile. Validation data showed good linearity (r2 >0.98), precision (%RSDs<3.4), and accuracy (recoveries ranging from 98.0 to 102.0%). The detection and quantitation limits are in the range of 6.0-8.5 and 18-25μM, respectively. The validation data is comparable to reported methods, however, the current method offers better precision with enhanced sensitivity (up to six times). Applications of the method show percent labeled amounts found in the studied samples within 100.6-109.3%, which complied with the United States Pharmacopeia limit (90.0-110.0%). The method was simple, rapid and, automated, which required no extra instrumentation or skillful operators.