Pelletized dosage forms can be prepared by different methods which, in general, are time consuming and labor intensive. The current study was carried out to investigate the feasibility of preparing the spherical pellets of omeprazole by sieving-spheronization. An optimized formulation was also prepared by extrusion-spheronization process to compare the physical parameters between these two methods. The omeprazole pellets were consisted of microcrystalline cellulose, polyvinylpyrrolidone K 30, sodium lauryl sulphate and polyethylene glycol 6000. The omeprazole delay release system was developed by coating the prepared pellets with aqueous dispersion of Kollicoat 30 DP. The moisture content, spheronization speed and residence time found to influence the final properties of omeprazole pellets prepared by extrusion-spheronization and sieving-spheronization. The Mann-Whitney test revealed that both methods produced closely similar characteristics of the pellets in terms of, friability (p=0.553), flowability (p=0.677), hardness (p=0.103) and density (bulk, p=0.514, tapped, p=0.149) except particle size distribution (p=0.004). The percent drug release from the coated formulation prepared by sieving-spheronization and extrusion spheronization was observed to be 84.12 ± 1.10% and 82.67 ± 0.96%, respectively. Dissolution profiles of both formulations were similar as indicated by values of f1 and f2, 1.52 and 89.38, respectively. The coated formulation prepared by sieving-spheronization and commercial reference product, Zimore ® also showed similar dissolution profiles (f1=1.22, f2=91.52). The pellets could be prepared using sieving-spheronization. The process is simple, easy, less time- and labor-consuming and economical as compared to extrusion-spheronization process.
Medications given via the intravenous (IV) route provide rapid drug delivery to the body. IV therapy is a complex process requiring proper drug preparation before administration to the patients. Therefore, errors occurring at any stage can cause harmful clinical outcomes to the patients, which may lead to morbidity and mortality. This was a prospective observational study with the objectives to determine whether medication errors occur in IV drug preparation and administration in Selayang Hospital, determining the associated factors and identifying the strategies in reducing these medication errors. 341 (97.7%) errors were identified during observation of total 349 IV drug preparations and administrations. The most common errors include the vial tap not swabbed during prepreparation and injecting bolus doses faster than the recommended administration rate. There was one incident of wrong drug attempted. Errors were significantly more likely to occur during administration time at 8.00am and when bolus drugs were given. Errors could be reduced by having proper guidelines on IV procedures, more common use of IV infusion control devices and by giving full concentration during the process. Awareness among the staff nurses and training needs should be addressed to reduce the rate of medication errors. Standard IV procedures should be abided and this needs the cooperation and active roles from all healthcare professionals as well as the staff nurses.
Study site: Hospital Selayang, Kuala Lumpur
The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.
In the present study, a sensitive and fully validated liquid chromatography with mass spectrometry method was developed for the quantification of three potential genotoxic impurities in rabeprazole drug substance. The separation was achieved on Symmetry C18 column (100 × 4.6 mm, 3.5 μm) using 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B in gradient elution mode at 0.5 mL/min flow rate. Triple quadrupole mass detection with electrospray ionization was operated in selected ion recording mode for the quantification of impurities. The calibration curves were demonstrated good linearity over the concentration range of 1.0-4.5 ppm for O-phenylenediamine, 1.8-4.5 ppm for 4-nitrolutidine-N-oxide and 1.0-4.5 ppm for benzyltriethylammonium chloride with respect to 10 mg/mL of rabeprazole. The correlation coefficient obtained in each case was >0.998. The recoveries were found satisfactory over the range between 94.22 and 106.84% for all selected impurities. The method validation was carried out following International Conference on Harmonization guidelines, from which the developed method was able to quantitate the impurities at 1.0 ppm for O-phenylenediamine, 1.8 ppm for 4-nitrolutidine-N-oxide and 1.0 ppm for benzyltriethylammonium chloride. Furthermore, the proposed method was successfully evaluated for the determination of selected impurities from bulk drug and formulation samples of rabeprazole within the acceptable limits.
Pharmaceutical excipients are no longer inert materials but it is effective and able to improve the characteristics of the products' quality, stability, functionality, safety, solubility and acceptance of patients. It can interact with the active ingredients and alter the medicament characteristics. The globalization of medicines' supply enhances the importance of globalized good manufacturing practice (GMP) requirements for pharmaceutical excipients. This review was intended to assess the globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients. The review outcomes demonstrate that there is a lack of accurately defined methods to evaluate and measure excipients' safety. Furthermore good manufacturing practice requirements for excipients are not effectively globalized.
Tension stiffening is a characteristic behavior of reinforced concrete (RC) beams which is directly affected by the bond-slip property of steel bar and concrete interfaces. A beam strengthened with a near-surface mounted (NSM) technique would be even more affected by tension stiffening, as the NSM reinforcement also possess a bond-slip property. Yet assessing how much the tension stiffening of NSM contributes to the behavior of RC beams is difficult due to the fact that bond-slip effects cannot be directly incorporated into a strain-based moment-curvature analysis. As such, the tension stiffening is typically incorporated through various empirical formulations, which can require a great deal of testing and calibrations to be done. In this paper a relatively new method, which can be called the mechanics-based segmental approach, is used to directly simulate the tension stiffening effect of NSM reinforcements on RC beams, without the need for empirical formulations to indirectly simulate the tension stiffening. Analysis shows that the tension stiffening of NSM fiber reinforced polymer (FRP) contributes a significant portion to the stiffness and strength of the strengthened RC beam not only during serviceability, but at all load levels.
The present work was aimed to investigate the effect of drying methods (oven drying, foam mat drying) and temperatures (40°C, 60°C) on the nutritional characteristics of red- and yellow-watermelon rinds. It was found that foam mat drying produced the best results for preserving the most nutrients as compared to the conventional oven drying for both red- and yellow watermelon rinds. Temperature is a significant parameter that affects the nutritional characteristics of watermelon rinds powder for both methods. Finding suggests that foam mat drying at 40°C was the best method for producing watermelon rinds powder as it requires shorter treatment time and gave the best retention of protein and carbohydrate.
This paper considers the problem of outlier detection in bilinear time series data with special focus on BL(1,0,1,1) and BL(1,1,1,1) models. In the previous study, the formulations of effect of innovational outlier on the observations and residuals from the process had been developed and the corresponding least squares estimator of outlier effect had been derived. Consequently, an outlier detection procedure employing bootstrap-based procedure to estimate the variance of the estimator had been proposed. In this paper, we proposed to use the mean absolute deviance and trimmed mean formula to estimate the variance to improve the performances of the procedure. Via simulation, we showed that the procedure based on the trimmed mean formula has successfully improved the performance of the procedure.
Co-crystal is an attractive alternative and a new class of solid forms because that can be engineered to have desired physicochemical properties. Co-crystals have gained considerable attention from the generic pharmaceutical industry after the USFDA released its finalized guidlines in the year 2018 on the regulatory classification of co-crystals. In this review, we discussed how co-crystals could be explored as a potential alternative solid form for the development of a generic product that meets the legal, regulatory, and bioequivalence requirements. In the contents, we discussed in detail concepts such as the selection of coformers, various ways of making co-crystals, the strategy of characterization to discriminate between co-crystal and salt, polymorphism in co-crystals, the aspects of intellectual property and, finally, the regulatory aspects of co-crystals.
The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO(2) flow rate, and the liquid phase flow rate on particle size and its distribution.
Orodispersible tablets disintegrate rapidly (within 3 minutes) in the oral cavity and release the medicament before swallowing. The mode of disintegrant addition might affect the properties of orodispersible tablets. The objective of this study was to formulate and evaluate orodispersible tablets by studying different modes of disintegration addition with varying concentrations of disintegrants. The wet granulation method was used to produce the orodispersible tablets. Two methods of disintegration addition were compared (i.e., intragranular, extragranular). Three disintegrants (i.e., cornstarch, sodium starch glycolate, crospovidone) were used at three levels (5%, 10%, and 15%) in the study. The formulations were tested for the powder flowability (angle of repose) and characterized physically (hardness, weight, thickness, friability, disintegration time). The mangosteen pericarp extract was used as a model active pharmaceutical ingredient to be incorporated into the optimum formulation. It was observed that the extragranular method produced granules with better flowability compared to that of the intragranular method. Crospovidone was found as the most efficient disintegrant among the three. The optimum formulation selected was one with the highest concentration of crospovidone (15%), which showed the fastest disintegration time. The mode of disintegrant addition into the orodispersible tablets formulation was found to show a marked difference in the disintegration, as well as other physical characteristics of the orodispersible tablets where the extragranular mode of addition showed better property, which caused the orodispersible tablets to disintegrate the fastest.
Nanoprecipitation is a simple and increasingly trending method for nanoparticles preparation. The self-assembly feature of poly (ethylene glycol)-poly (lactide-co-glycolic acid) (PEG-PLGA) amphiphilic copolymer into a nanoparticle and its versatile structure makes nanoprecipitation one of the best methods for its preparation. The aim of this study is to review currently available literature for standard preparation of PEG-PLGA nanoparticles using nanoprecipitation technique in order to draw conclusive evidenceto draw conclusive evidence that can guide researchers during formulation development. To achieve this, three databases (Web of Science, Scopus and PubMed) were searched using relevant keywords and the extracted articles were reviewed based on defined inclusion and exclusion criteria. Data extraction and narrative analysis of the obtained literature was performed when appropriate, along with our laboratory observations to support those claims wherever necessary. As a result of this analysis, reports that matched our criteria conformed to the general facts about nanoprecipitation techniques such as simplicity in procedure, low surfactants requirement, narrow size distribution, and low resulting concentrations. However, these reports showed interesting advantages for using PEG-PLGA as they are frequently reported to be freeze-dried and active pharmaceutical ingredients (APIs) with low hydrophobicity were reported to successfully be encapsulated in the particles.
Orally disintegrating tablets are a solid dosage form that will disintegrate rapidly within 3 minutes upon contact with saliva. Fillers or diluents are excipients that are used to make up the volume of orally disintegrating tablets, and some might act as a disintegrant or binder that will affect the physical properties of orally disintegrating tablets. The objective of this study was to formulate and evaluate physical properties of orally disintegrating tablets containing Annona muricata leaves extract by a freeze-drying method using different fillers at different concentrations. In this study, fifteen formulations of orally disintegrating tablets were prepared by a freeze-drying method with different fillers such as starch, lactose, microcrystalline cellulose, StarLac, and CombiLac at 5%, 10%, and 15%. The orally disintegrating tablets were evaluated for hardness, thickness, weight variation, friability, and disintegration time test. The optimum formulation was chosen and incorporated with Annona muricata leaves extract. The results obtained in this work indicated that Formulation 3, with 15% starch, was the most optimum formulation due to the shortest disintegration time (21.08 seconds ± 4.24 seconds), and all the physical tests were within the acceptable range. The orally disintegrating tablets containing Annona muricata leaves extract possessed antioxidant activity and stable at least for 3 months under 60°C and 75% relative humidity.
This paper describes the preparation, characterisation, and potential application of flexible palm oil-based polyurethane foam (PUF) as a support for iron-silica (Fe-Si) adsorbent. Fe-Si/polyurethane composite (Fe-Si/PUC) was prepared by impregnating Fe-Si adsorbent onto the surface of PUF by using a novel immersion-drying method. Morphological analysis of Fe-Si/PUC proved that Fe-Si was successfully impregnated onto the surface of PUF. Compression test and thermogravimetric analysis were carried out to determine the flexibility and thermal stability of Fe-Si/PUC, respectively. The Fe-Si/PUC removed 90.0% of 10 ppm methylene blue (MB) from aqueous solution in 60 min. The reusability study showed that Fe-Si/PUC removed 55.9% of MB on the seventh cycle. Hence, the synthesis of Fe-Si/PUC opens up a new path of implementing palm oil-based PUF to assist in the recovery of an adsorbent for environmental clean-up. The mechanism of physical interaction during the impregnation of Fe-Si adsorbent onto PUF was proposed in this paper.
Drug delivery constitutes the formulations, technologies, and systems for the transport of pharmaceutical compounds to specific areas in the body to exert safe therapeutic effects. The main criteria for selecting the correct medium for drug delivery are the quantity of the drug being carried and the amount of time required to release the drug. Hence, this research aimed to improve the aforementioned criteria by synthesizing a medium based on calcium carbonate-nanocellulose composite and evaluating its efficiency as a medium for drug delivery. Specifically, the efficiency was assessed in terms of the rates of uptake and release of 5-fluorouracil. Through the evaluation of the morphological and chemical properties of the synthesized composite, the established 3D printing profiles of nanocellulose and CaCO3 took place following the layer-by-layer films. The 3D printed double laminated CaCO3-nanocellulose managed to release the 5-fluorouracil as an effective single composition and in a time-controlled manner.
Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.
The susceptibility of probiotics to low pH and high temperature has limited their use as nutraceuticals. In this study, enhanced protection of probiotics via microencapsulation was achieved. Lactobacillus plantarum LAB12 were immobilised within polymeric matrix comprised of alginate (Alg) with supplementation of cellulose derivatives (methylcellulose (MC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC)). L. plantarum LAB12 encapsulated in Alg-HPMC(1.0) and Alg-MC(1.0) elicited improved survivability (91%) in simulated gastric conditions and facilitated maximal release (∼100%) in simulated intestinal condition. Alg-HPMC(1.0) and Alg-MC(1.0) significantly reduced (P 7 log CFU g-1. Alg-MC and Alg-HPMC improved the survival of LAB12 against simulated gastric condition (9.24 and 9.55 log CFU g-1, respectively), temperature up to 90 °C (9.54 and 9.86 log CFU g-1, respectively) and 4-week of storage at 4 °C (8.61 and 9.23 log CFU g-1, respectively) with sustained release of probiotic in intestinal condition (>9 log CFU g-1). These findings strongly suggest the potential of cellulose derivatives supplemented Alg bead as protective micro-transport for probiotic strains. They can be safely incorporated into new functional food or nutraceutical products.
Matched MeSH terms: Drug Compounding/instrumentation; Drug Compounding/methods*
Electrodeposition is commonly used to deposit ceramic or metal coating on metallic implants. Its utilization in depositing polymer microcapsule coating is currently being explored. However, there is no encapsulation of drug within polymer microcapsules that will enhance its chemical and biological properties. Therefore, in this study, ginseng which is known for its multiple therapeutic effects was encapsulated inside biodegradable poly(lactic-co-glycolic acid) (PLGA) microcapsules to be coated on pre-treated medical grade stainless steel 316L (SS316L) using an electrodeposition technique. Polyaniline (PANI) was incorporated within the microcapsules to drive the formation of microcapsule coating. The electrodeposition was performed at different current densities (1-3 mA) and different deposition times (20-60 s). The chemical composition, morphology and wettability of the microcapsule coatings were characterized through attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM) and contact angle analyses. The changes of electrolyte colors, before and after the electrodeposition were also observed. The addition of PANI has formed low wettability and uniform microcapsule coatings at 2 mA current density and 40 s deposition time. Reduction in the current density or deposition time caused less attachment of microcapsule coatings with high wettability records. While prolonging either one parameter has led to debris formation and melted microcapsules with non-uniform wettability measurements. The color of electrolytes was also changed from milky white to dark yellow when the current density and deposition time increased. The application of tolerable current density and deposition time is crucial to obtain a uniform microcapsule coating, projecting a controlled release of encapsulated drug.
Matched MeSH terms: Drug Compounding/instrumentation; Drug Compounding/methods