Drug Stability

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Didactic Strategy for Students to Prepare a Protocol to Conduct a Drug Stability Study

Didactic Strategy for Students to Prepare a Protocol to Conduct a Drug Stability Study

Abstract The results of a didactic strategy Workshop application in the course of Pharmaceutical Physicochemistry II are presented. This strategy allows building knowledge significantly when establishing a relationship with personal experience. The knowledge and application of the current regulations for the development of drug stability studies in Costa Rica, is a fundamental aspect of the pharmacist`s work in this country. For this reason, in this course which is taught in the third year of the pharmacy career at the University of Costa Rica, the topic is included when the issue of drug stability is developed. This activity proposed a new way of approaching the issue, involving the student in the construction of a more meaningful knowledge, by management and application of the stability norms developing along the semester in five stages: 1) plan the strategy, 2) coordination between the teachers of the different laboratory groups, 3) knowledge of the basic concepts of stability by students, 4) application of the teaching strategy in two laboratory sessions and 5) evaluation of the strategy by students, through the Google Forms platform. The work teams reviewed the Central American Technical Regulations (RTCA) and developed the stability protocol for the assigned drugs. Subsequently, they presented their proposals at the indicated time. Conclusion: The strategy used was very successful for the development of the issue of regulatory aspects of drug stability, since it aroused the interest of most students and validates the need to conduct coordination meetings between teachers.
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An Approach to Drug Stability Studies and Shelf-life Determination

An Approach to Drug Stability Studies and Shelf-life Determination

The Shelf life of the pharmaceutical drug products is established by the stability studies. Stability testing of pharmaceuticals is known to be a complex set of procedures which involves significant cost, time and scientific proficiency to generate safety, in quality and efficacy in a drug formulation. The understanding of the drug development process and the infinite tasks and milestones that is essential to abroad development plan result in scientific as well as commercial success of any pharmaceutical product [1]. Stability defines as “The capability of a particular formulation in a specific container/closed system, to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications throughout its shelf life”. Stability is officially defined as "the time lapse during which the drug product retains the same properties & characters that are processed at the time of manufacture” [2]. The various factors affecting the stability of a pharmaceutical product; because of their involvement, stability testing is known as a complex process. These factors mostly concern the stability of the active ingredient(s); interaction of active ingredients and excipients, type of dosage form and their manufacturing process followed, container/closure system used for packaging, heat, moisture and light come across during shipment, storage and handling etc. [3]. The shelf-life determination of the drug product is the main objective of stability studies. The stability refers to storage time allowed before any degradation product in dosage form achieves a sufficient level to represent a risk to the patient. Based on this time, the product shelf life or expiration date is determined [4]. From a pharmaceutical development point of view, stability studies are frequently on the critical path to starting patient studies and registration stability studies, as described in the International Conference on Harmonization (ICH) guideline Q1A (R2), are commonly the activity on the critical path to regulatory filing and approval. Stability studies are also a significant resource
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A Robust Liquid Chromatographic Method for Confirmation of Drug Stability of Azithromycin in Bulk Samples, Tablets and Suspensions

A Robust Liquid Chromatographic Method for Confirmation of Drug Stability of Azithromycin in Bulk Samples, Tablets and Suspensions

the UV detector since the electrodes have direct contact with column effluent and may react with sample matrix while polymer columns are relatively more expensive compared to silica-based columns. This calls for use of pH and temperature stable strategies to improve on column longevity, stability and peak parameters. Such a method can be used for routine quality control of azithromycin bulk samples and formulations as well as market surveillance of samples. A reverse phase high performance liquid chromatographic method for the estimation of azithromycin suspension described by Sachin et al. [15] did not exhibit the required specificity regarding the related substances, NDMAZT, AZA, DAZT, EAOX and EAIE while the gradient method proposed by Miguel et al. [16] suffers from baseline instability and uses a slightly high temperature of 50 °C. This paper describes the development, validation and application of a selective, isocratic and robust liquid chromatographic method for the analysis of azithromycin in bulk samples and oral dosage forms.
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 ENHANCEMENT OF BIOAVAILABILITY THROUGH INCREASE IN DRUG PERMEATION, STABILITY AND RETENTION TIME

 ENHANCEMENT OF BIOAVAILABILITY THROUGH INCREASE IN DRUG PERMEATION, STABILITY AND RETENTION TIME

The rate and extent to which an unchanged drug reaches the systemic circulation is called as bioavailability (BA). Bioavailability, a subcategory of absorption is one of the principal pharmacokinetic parameter determined for an active substance form a pharmaceutical product. It also indicates the fractional extent to which a dose of drug reaches its site of action or biological fluid from which the drug has access to its site of action. Physical properties of drug, drug formulation, route of administration, gastric emptying rate etc. are several factors affect the bioavailability of drug from its drug product. Poor solubility, enzymatic and transporters barrier, drug stability and short retention of the drug in stomach due to peristaltic movement are several factors decrease the bioavailability of the drug. This review deals with the bioavailability improvements techniques from poor permeation, lesser stability and short retention of the drug in stomach. Lipid based formulations; ion pairing and use of permeation enhancer are different methods to enhance the bioavailability through increase in permeation. Enteric coating, complexation and metabolism inhibitors lead to increase in drug stability. Bioadhesive polymers in formulation improve the gastro retention time serve as improved bioavailable product.
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A Stability Indicating UPLC Method for Candesartan in Bulk Drug Samples

A Stability Indicating UPLC Method for Candesartan in Bulk Drug Samples

Candesartan was approved by the FDA in 1998 [1-6]. Few LC methods were reported in the literature for the analysis in biological samples [8]. Extensive literature survey reveals there is no stability indicating UPLC method for determination of related substances and quantitative estimation of Candesartan in bulk drugs and pharmaceutical dosage forms. An ideal stability indicat- ing chromatographic method should estimate the drug to be able to resolve from its potential impurities and deg- radation products. The present drug stability test guide line Q1A (R2) issued by International Conference on Harmonization (ICH) suggested that stress studies should be carried out on a drug to establish its inherent stability characteristic, leading to separation of degradation prod- ucts and hence supporting the stability of the proposed analytical procedures. It also requires that analytical test procedures for stability samples should be stability indi- cating and they should be fully validated [9].
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NANOTECHNOLOGICAL APPROACH TO ENHANCE THE STABILITY AND BIOAVAILABILITY OF THE HERBAL DRUG "MURVA"

NANOTECHNOLOGICAL APPROACH TO ENHANCE THE STABILITY AND BIOAVAILABILITY OF THE HERBAL DRUG "MURVA"

quick release of drug. Stability studies confirmed that all the nanoparticles preparations were stable at room temperature and or less may be more suitable for stability purpose. Hence it can be concluded that the newly developed formulation- nanoparticulate drug delivery system of murva with Chitosan is considered to be potential and effective agent to enhance the bioavailability and stability.

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Multiple linear regression modelling to predict the stability of polymer drug solid dispersions: comparison of the effects of polymers and manufacturing methods on solid dispersion stability

Multiple linear regression modelling to predict the stability of polymer drug solid dispersions: comparison of the effects of polymers and manufacturing methods on solid dispersion stability

Solid dispersions can be a successful way to enhance the bioavailability of poorly soluble drugs. Here 60 solid dispersion formulations were produced using ten chemically diverse, neutral, poorly soluble drugs, three commonly used polymers, and two manufacturing techniques, spray drying and melt extrusion. Each formulation underwent a six-month stability study at accelerated conditions, 40 °C and 75% relative humidity (RH). Significant differences in times to crystallisation (onset of crystallisation) were observed between both the different polymers and the two processing methods. Stability from zero days to over one year was observed. The extensive experimental dataset obtained from this stability study was used to build multiple linear regression models to correlate physicochemical properties of the active pharmaceutical ingredients (API) with the stability data. The purpose of these models is to indicate which combination of processing method and polymer carrier is most likely to give a stable solid dispersion. Six quantitative mathematical multiple linear regression-based models were produced based on selection of the most influential independent physical and chemical parameters from a set of 33 possible factors, one model for each combination of polymer and processing method, with good predictability of stability. Three general rules are proposed from these models for the formulation development of suitably stable solid dispersions. Namely, increased stability is correlated with increased glass transition temperature (T g ) of solid
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Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

response to the GSH stimulus at the tumor sites. Therefore, FA-CCM-Cur, which combined folate receptor-mediated active targeting drug delivery with the stable drug delivery during circulation endowed by the core cross-linking, showed the highest (at all the time points) and the longest (even 48 hours after injection) Cur accumulation in tumor. Mean- while, we found that a relatively higher accumulation in the liver was observed compared to that in other organs, which is likely due to the nonspecific accumulation or clearance of nanoparticles by the reticuloendothelial system. Meanwhile, FA-CCM was also dissolved in liver, which was caused by high GSH concentrations in liver. The statistical results of Cur accumulated livers in the three micelles showed no significant differences (Figure 9C).
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Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability

Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability

There have been several national surveys that have attempted to identify commonly used mixtures [3–6]. These studies, however, are several years old and do not reflect current practice. The most recent survey of CSCI use in the UK was performed over a decade ago in 2004 [6]. The majority of combinations contained either two or three drugs (44 and 30% respectively) and an opioid was invariably a component. The authors concluded that compatibility and stability data were unavailable for more than half of the frequently used combinations. This is unsurprising for two reasons. Firstly, laboratory analysis is expensive and laborious. Secondly, the num- ber of potential combinations is vast; Dickman et al. [2] identified 35 drugs that could be administered by CSCI, 11 of which were opioids. Based on these figures, there are theoretically 142,450 combinations (Fig. 1). Of course, certain combinations of drugs are impractical, so the number of clinically useful combinations is signifi- cantly lower. For example, for five non-opioids and one opioid, there are potentially 56 combinations comprising up to five drugs.
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A Novel Validated Stability-indicating HPTLC Method to Quantitate Forskolin as a Bulk Drug and in a Nanosuspension

A Novel Validated Stability-indicating HPTLC Method to Quantitate Forskolin as a Bulk Drug and in a Nanosuspension

be 94.1 % with a % RSD of 0.0357 for three replicates. The suitability of the method is indicated by low value of % RSD and thus, can be used for routine analysis of forskolin in various dosage forms. No degradation of the drug occurred in formulation as the developed chromatogram showed a single peak of drug with little or no interference of the excipients during the analysis. Additional peaks at different R f values were obtained for the chromatograms of the acid-degraded samples and base-degraded samples. Three peaks for acid- induced degraded sample were observed at R f values 0.12, 0.37, 0.39 as shown in Table 6 and fig. 4a while for base-induced degraded sample two peaks were observed at R f values 0.02 and 0.57 as shown in Table 6 and fig. 4b. The forskolin spot was well resolved from the degraded products from acid and base-induced degradation. The three additional peaks apart from forskolin peak were obtained as degraded product peaks from hydrogen peroxide 30 % v/v treatment
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Stability Matrix Designs: A Boon For Stability Testing of Pharmaceutical Drug Products.

Stability Matrix Designs: A Boon For Stability Testing of Pharmaceutical Drug Products.

Long term stability is done in a matrix approach after manufacturing of drug for ensuring the stability of drugs. Using the matrix basic design which is useful for testing 3 lots under one storage condition can be expanded to multiple presentation of products or multiple storage conditions. The design shows full testing at the end points (0 and 36 months) and shows partial testing at the interim time points (3, 6, 9, 12, 18 &24 min). With the assistance of a statistical search algorithm, the test points are selected . 37.5% reduction in analytical testing, while permitting a reliable interim expiry estimate. Based on 12 months stability data it is provided by the proposed matrix design. The matrix approach obtained by expiration dating periods is typically more conservative than the approaches derived from the full testing estimate. The comparison of expiration dating estimate for meter dose inhaler and capsules is presented using the matrixed and full testing approaches. Keywords: Matrix Design, Stability, Expiration Dating
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STABILITY INDICATING RP UHPLC METHOD FOR DETERMINATION OF TELMISARTAN IN DRUG SUBSTANCE AND MARKETED FORMULATION

STABILITY INDICATING RP UHPLC METHOD FOR DETERMINATION OF TELMISARTAN IN DRUG SUBSTANCE AND MARKETED FORMULATION

Telmisartan standard drug was obtained as a gift sample from Micro lab, Bengaluru, India, ammonium acetate from Merck, India, acetic acid from Spectrochem, sodium dihydrogen orthophosphate dehydrate from Fisher Scientific, hydrochloric acid, sodium hydroxide, hydrogen peroxide, (AR grade) from Sd fine-chem. limited, acetonitrile (HPLC grade)was obtained from Spectrochem and methanol (HPLC grade) was obtained from Finar, India. Mill Q HPLC water was used for all purposes. Telmisartan tablet label

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Stability Indicating HPTLC Determination of Triamcinalone Acetonide in Bulk Drug and Sterile Injectable Suspension

Stability Indicating HPTLC Determination of Triamcinalone Acetonide in Bulk Drug and Sterile Injectable Suspension

subjected to acid, alkali and neutral hydrolysis, oxidation, sun light and dry heat treatment. The degraded products were well separated from the pure drug with notably different R f values. CAMAG semi-automatic HPTLC used for the analysis. Densitometric analysis of TRIA was carried out in the absorbance mode at 240 nm. The linear regression data for the calibration plots showed good linear relationship with correlation coefficient 0.9996 ±/ 0.001 in the concentration range of 100.0-2000.0 ng spot -1 . The values of

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Adhesion characteristics and stability assessment of lectin modified liposomes for site specific drug delivery

Adhesion characteristics and stability assessment of lectin modified liposomes for site specific drug delivery

Carbohydrate moieties of the cellular glycocalyx have been suggested to play an important role in biological recognition processes during pathologic conditions, such as inflammation and cancer. Herein, we describe lectin-modified liposomes which might have potential for site- specific drug delivery during the therapy of such diseases. Specific interactions of plain (i.e., unmodified) and PEGylated, lectin-grafted liposomes with model membranes were investigated under real-time flow conditions using a quartz crystal microbalance. In addition, the morphology of the liposomal systems was assessed by atomic force microscopy. Plain liposomes exhibited only unspecific adhesion to glycolipid membranes and had a tendency to coalesce. The degree of membrane interaction was significantly increased when plain liposomes were modified with the lectin, Concanavalin A. However, vesicle fusion also markedly increased as a result of lectin modification. Additional PEGylation of liposomes reduced unspecific adhesion phenomena, as well as coalescence. Moreover, our studies enabled us to establish quartz crystal microbalance and atomic force microscopy as powerful and complementary methods to characterize adhesion properties of targeted drug delivery systems.
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A novel liquid oral formulation for 1- Octacosanol an anticancer drug and its stability study

A novel liquid oral formulation for 1- Octacosanol an anticancer drug and its stability study

Numerous trials were conducted in order to ensure a biocompatible, physically stable primary emulsion. Apparently, t h e F1 emulsion got separated within a few minutes of the formation. In the case of F2, the emulsion was formed, but it was too thick and difficult to handle. On the other hand, the F3 emulsion was formed using cremophor, but the stability was only momentary. In the F4 formulation, the emulsion was formed, but it was too thick and it was felt that the addition of higher water quantity could dilute the same. In view of the above inferences from formulation F1 to F4, the possibility of forming a primary emulsion by integrating the HLB (Hydrophilic Lipophilic Balance) values of the oil and oil phase emulsifier was explored. In theF5 emulsion, both Span-20, an emulsifier and corn oil, an oil phase possess the HLB value of 8.6, and through the primary preparation process, it was found to be a reasonably stable emulsion. Incorporation of the active into the primary emulsion was carried out and in this case, F5 was chosen as the base formula and the same method was used to create F6. The experiment indicated the instability of the emulsion system in the presence of 1-Octacosanol. The pH of the emulsion was adjusted to7.01. In the case of F7, the emulsion was separated out due to imbalance of emulsifier and oil. The F8 emulsion formed frothing. In the F9, the emulsion separated within five hours of the formation. The emulsion with soybean oil was found to be very thick; hence, it is inferred that corn oil is the better option when compared to soybean oil. In the F10 formulation, the emulsion was separating out with some settling within two weeks of its formation. In the F11 formulation, the emulsion was formed, but it was dull and frothy. In the F12, the emulsion was formed, but dull in colour and the same separated within a week. In the F13 formulation,
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New stability-indicating liquid chromatographic method for determination of palbociclib (an anti-breast cancer drug)

New stability-indicating liquid chromatographic method for determination of palbociclib (an anti-breast cancer drug)

For peroxide degradation, 2.5 ml of drug solution was taken into a 25 ml volumetric flask and diluted with 10 ml of mobile phase. This solution was sonicated for 30 min and then treated with 5 ml of 30% hydrogen peroxide. Later, it was heated on a thermostat at 80°C for 30 min and cooled to room temperature. The resultant solution mixture was filtered through 0.45 µ membrane filter. 20 µL of this solution was injected into the system, and the peak area was noted from the corresponding chromatogram.

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Determination Of Assay And Validation Of Stability Indicating RP-HPLC Method For Ganciclovir In Nciclovir Drug Substance

Determination Of Assay And Validation Of Stability Indicating RP-HPLC Method For Ganciclovir In Nciclovir Drug Substance

The goal of this artwork is, to expand a easy and rapid technique for the willpower of assay of Ganciclovir in Ganciclovir drug substance via way of using HPLC system. Method development become initiated with Ganciclovir drug substance solubility look at, primarily based mostly on that water turned into selected as diluent for diluting all of the answers of Ganciclovir. From the molecular components of Ganciclovir, it was observed that Gancicloviris polar in nature, based on that non- polar Hypersil BDS C18 table certain section column changed into decided on for developing RP- HPLC technique. Ganciclovir answer pH become 6.7 (C is 1 %weight/volume, in water, at 25°C), primarily based on that buffer end up selected pH 5.3 (pH about ± 2.0 w.r.t determined pH 6.7). BDS C18, 150 mm x four.6mm, 5.0µm particle diameter column with dibasic potassium dihydrogen ortho phosphate buffer (0.01M, pH:5.Three) as As there's chromophore located in Ganciclovir, there may be opportunity for UV-Visible detection, based totally on the colour absorbance take a look at 245 nm changed into decided on for monitoring the response of Ganciclovir. Preliminary take a look at became performed via the usage of Hypersil mobile section, added in an iso-caratic approach with a glide rate of one mL min-1 at ambient temperature and analytes had been monitored with PDA detector, no any top became eluted upto forty mins. Elution of analyte became finished, with the combination of phosphate buffer (0.01M, pH:5.Three) and acetonitrile within the ratio of 60:forty% (v/v). In this trial Ganciclovir height became eluted at about 2 or 3 minutes and interfering with unknown height eluted at about 2 min and additionally sizeable top shapes were decided. For higher selection, trial turned into made with PO₄ buffer (0.01M, pH:5.3) with acetonitrile in the ratio of 70:30% (v/v), peaks had been well resolved from
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Stability, Hopf bifurcation and effects of impulsive antibiotic treatments in a model of drug resistance with conversion delay

Stability, Hopf bifurcation and effects of impulsive antibiotic treatments in a model of drug resistance with conversion delay

9. Sirinukunwattana, K., Lenbury, Y., Tumrasvin, N.: Drug resistant and wild-type strains interaction: investigating effects of conversion delays for possible control strategies. Int. J. Math. Models Methods Appl. Sci. 4, 830–838 (2011) 10. Rodríguez, G.: Lecture Notes on Generalized Linear Models (2007). http://data.princeton.edu/wws509/notes/ 11. Culshaw, R.V., Ruan, S.: A delay-differential equation model of HIV infection of CD4+ T-cells. Math. Biosci. 165, 27–39

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Validated Gradient Stability Indicating UPLC Method for the Determination of Related Substances of Posaconazole in Bulk Drug

Validated Gradient Stability Indicating UPLC Method for the Determination of Related Substances of Posaconazole in Bulk Drug

Posaconazole (POS) 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3- furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4- triazol-3-one (Figure 1) [1]. Available under the brand names Noxafil oral suspension (40 mg per mL) and Noxafil 100 mg Gastro-resistant tablets [2] from the MSD (Merck Sharp & Dohme Ltd, Hertford Road, Hod- desdon Hertfordshire EN11 9BU United Kingdom)-Used for the Prevention of invasive Aspergillus and Candida infections in severely immune compromised adults and adolescents ≥13 years of age, including hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host-disease (GVHD) and patients with hematologic malignancies and prolonged chemotherapy-associated neutropenia [3]-[5]. The administration of drug is done orally during or immediately following a full meal or liquid nutritional supplement. Alternatively may be ad- ministered with an acidic beverage. Has been administered via nasogastric (NG) tube [6] closely monitor such patients for breakthrough fungal infections since systemic exposure may be lower and may be associated with an increased risk of treatment failure.
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STABILITY-INDICATING RP-HPLC METHOD FOR ANALYSIS OF EMTRICITABINE IN THE BULK DRUG AND IN A PHARMACEUTICAL DOSAGE FORM

STABILITY-INDICATING RP-HPLC METHOD FOR ANALYSIS OF EMTRICITABINE IN THE BULK DRUG AND IN A PHARMACEUTICAL DOSAGE FORM

The method was validated for linearity, specificity, limits of detection (LOD) and quantification (LOQ), system suitability, accuracy, precision, robustness and stability in accordance with ICH guidelines. To assess specificity, peak purity was determined by use of the photodiode-array detector. To check linearity, test solutions of EMT were prepared at six concentrations 5-25μg/ml. Each solution was injected in triplicate and calibration graphs were obtained by plotting peak area against concentration. Linearity was checked over the same concentration range on three consecutive days. RSD (%) of the slope and Y-intercept of the calibration plot were also calculated. The limits of detection(LOD) and quantification (LOQ) for EMT were determined, as the amounts for which signal-to-noise ratios were 3:1 and 10:1, respectively, by injecting a series of dilute solutions of known concentration. Precision, as RSD (%) was determined by measuring the concentration of drug in the injection six times. Intermediate (inter-day) precision was evaluated by two analysts on different days in the same laboratory. The accuracy of the method was studied by measurement of recovery after adding known amounts of the drug (80, 100 and 120% of the label claim of known amount of EMT per injection) to the placebo. Three samples were prepared for each recovery level and results were calculated by use of the calibration plot. The robustness of the method was assessed by deliberate alteration of the experimental conditions and determining the effect on resolution of EMT from the main product obtained
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