Moisture the dominant factor in the stability of doxylamine succinate tablets

During a stability trial at 55°C with doxylamine succinate combined with different excipients at different moisture contents, moisture was found to be the dominant factor affecting the stability of doxylamine succinate. Each excipient however also had a specific affect.     

Compatibility Study Between Doxylamine Succinate with Other Drugs and Excipients Using Differential Scanning Calorimetry

Abstract

Differential scanning calorimetry was used to investigate the interactions between doxylamine succinate and a number of drugs and excipients. Doxylamine succinate was found to be compatible with mannitol, Aerosil®, calcium salts, starches, Ac-Di-Sol®, Primojel® and Avicel®. Doxylamine succinate was found to be incompatible with acetominophen, dextromethorphan hydrobromide, codeine phosphate, pseudoephedrine hydrochloride, magnesium stearate, stearic acid, P.V.P. and lactose.     

The Effect of Environmental Moisture and Temperature on the Physical Stability of Effervescent Tablets in Foil Laminate Packages Containing Minute Imperfections

Abstract

The effect of environmental moisture on the physical stability of effervescent tablets in foil laminate packages containing microscopic imperfections (openings) was examined. Packaged tablets were stored at different relative humidity (RH) and temperature conditions and evaluated for physical stability at predetermined time intervals. Physical stability was assessed by noting if the tablet components reacted prematurely to yield soft tablets during storage. A penetrating dye solution test was used to determine if the foil packages contained imperfections which might allow transmission of moisture. The results of the investigation indicated that absolute moisture integrity of the foil package is required for product stability.     

Compatibility Study Between Doxylamine Succinate with Other Drugs and Excipients Using Differential Scanning Calorimetry

Differential scanning calorimetry was used to investigate the interactions between doxylamine succinate and a number of drugs and excipients. Doxylamine succinate was found to be compatible with mannitol, Aerosil®, calcium salts, starches, Ac-Di-Sol®, Primojel® and Avicel®. Doxylamine succinate was found to be incompatible with acetominophen, dextromethorphan hydrobromide, codeine phosphate, pseudoephedrine hydrochloride, magnesium stearate, stearic acid, P.V.P. and lactose.     

Stability of the Mokohydrate Crystal form of Cefazolin Sodium as a Function of Moisture

Abstract

Moisture effects on the stability of the monohydrate crystal form of cefazolin sodium were investigated. Results show that increased moisture content of this compound adversely affects the microbiological and polarographic stability at elevated temperatures. In addition, butyl rubber stoppers provided more protection against moisture than natural rubber stoppers at higher humidity conditions.     

The Stability of Aspirin in a Moisture Containing Direct Compression Tablet Formulation

Abstract

Studies were conducted on the stability of a direct compression tablet formulation containing aspirin as a model hydrolabile drug. Emdex^R (a mixed-sugar diluent containing approximately 8 percent moisture) and stearic acid (a lubricant) made up the remainder of the formulation. Both tablets and uncompressed powder blend were manufactured, packaged in storage containers and placed on stability at different storage temperatures. Stability samples were assayed for aspirin and salicylic acid using a stability indicating analytical method. Analysis of the stability data showed that the rate of aspirin decomposition accelerated with time. Also, the aspirin decomposition rate increased with temperature. The data were fit to the empirical equation y = 100 – ktⁿ, where y is the percent aspirin remaining, t is time, and k and n are constants. The formulation showed good stability, with less than one percent decomposition occuring after 1.75 years of storage at room temperature. This result indicates that although the aspirin formulation contained approximately 8 percent moisture, at room temperature the majority of the moisture present in the formulation is not available to react with the aspirin. The apparent activation energy of the solid-state aspirin decomposition was 46 kcal/mole, which is higher than expected. This result may be due to a temperature dependent release of moisture from the Emdex^R. Further studies are needed to verify this explanation.     

Factors influencing the properties and the stability of spray-dried Sennae fructus extracts

Objective: The objective of this study was to characterize the properties of aqueous Sennae fructus extracts prepared by spray-drying at varying process conditions.

Significance: From an industrial point of view it is essential to develop a formulation which has a constant quality over the whole period of its specified shelf-life.

Method: Sennae fructus extracts were spray-dried with different atomizing gas pressures, pump feed rates, and inlet temperatures. The extracts were analyzed for their physical properties and stored at accelerated conditions. Sennoside degradation was monitored by HPLC analysis.

Results: An increase of the atomizing gas pressure had the most pronounced influence on the decrease of moisture content and particle size. An increase of the inlet temperature led to a decrease of moisture content and particle density, as well as an increase of smooth particle amount. An increase in the pump feed rate, increased the moisture content and resulted in stable hollow spheres. The different conditions also led to smooth or wrinkled particle surfaces, and to golfball, donut, and shard particle shapes. The chemical stability of the sennosides differed from each other after storage. Stability-reducing factors were the moisture content of the samples and their hygroscopicities, as well as different particle morphologies. These factors were influenced by the inlet temperature of the spray-drying process. High inlet temperatures led to a positive influence on dryness and particle morphology and therefore on the stability of the sennosides.

Conclusions: Variation of the process conditions affected the resulting particle properties and their storage stability of Sennae fructus extract.     

Effervescent Tablets of Ascorbic Acid. I. Physical Study of the Possible components to Be Used

Abstract

The stability of ascorbic acid effervescent tablets is substantially affected by moisture. Therefore the choice of suitable excipients is a very important step in the formulation study of this type of tablets. This work reviews the most common excipients used in effervescent preparations. They are characterized by microscopical observation and determination of particle size distribution, density, moisture, hygroscopicity, and electrostatics. Hygroscopicity is the most important property when choosing an excipient for an effervescent preparation. Therefore, two different methods for its determination have been used.     

Urokinase: Stability Studies in Solution and Lyophilized Formulations

Abstract

Urokinase - a serine protease - is used clinically as a thrombolytic agent to dissolve blood clots. Low molecular weight Urokinase (33,000 dalton) isolated from human kidney cells using tissue culture techniques was used in the stability studies. Quantitative determination of Urokinase was accomplished by either amidolytic or fibrinolytic activity assay methods. The degradation of Urokinase in solution at 55 °C follows pseudo-first order kinetics at several pH values. The pH range for maximum stability has been determined to be about 6 to 7.

The stability of Urokinase is very sensitive to the quantity of residual moisture in the lyophilized formulation. Rubber stoppers used as closures for the glass vials were identified as a major source of moisture. The loss of activity from freeze dried formulations was inversely related to the specific activity of tissue culture derived Urokinase. Similar relationship was also observed for the adsorption of Urokinase from 5% dextrose diluent to the surface of polyvinyl chloride large volume parenteral diluent bags. Initial degradation rates (zero order) for freeze dried urokinase formulations with and without the addition of human serum albumin (HSA) as a stabilizer determined at 50, 40 and 30 °C demonstrated that loss of urokinase followed the Arrhenius relationship with an apparent energy of activation (Ea) of 15 kcal per mol. The addition of HSA resulted in an increase in stability by about a factor of four. However, the apparent Ea for the formulations with and without HSA was not significantly different as evident from parallel slopes in the Arrhenius plots.     

Stability of Ascorbic Acid-Zinc Sulphate Tablets

Abstract

Microencapsulation using ethylcellulose and embedding in stearic acid or polyethylene glycol 6000 have been employed to protect ascorbic acid from metallic ion catalysed oxidation in tablets containing zinc sulphate. It is observed that presence of Zn in the tablets do not affect stability of ascorbic acid even at accelerated storage conditions provided the moisture content is controlled.     

Effect of Moisture on the Stability of Solid Dosage Forms

Abstract

It has long been known that moisture affects the stability of some drug substances. Aspirin is a classical example. Aspirin is not wet granulated. Even though the water is driven off in a wet granulation, there is still sufficient moisture stress in the process to induce excessive decomposition on subsequent storage. Dry methods (slugging, roller compaction) are therefore resorted to. In other instances, the moisture sensitivity of a drug may warrant using a hard shall capsule approach. This presumes that the drug substance is not particularly hygroscopic, since, otherwise, the capsule shell will provide an unwanted source of moisture.     

Comparison of the relative stability of pharmaceutical cocrystals consisting of paracetamol and dicarboxylic acids

Objective: The aim of this study is to evaluate the relative stability of pharmaceutical cocrystals consisting of paracetamol (APAP) and oxalic acid (OXA) or maleic acid (MLA).

Significance: These observations of cocrystal stability under various conditions are useful coformer criteria when cocrystals are selected as the active pharmaceutical ingredient in drug development.

Method: The relative stability was determined from the preferentially formed cocrystals under various conditions.

Result: Cocrystal of APAP–OXA was more stable than that of APAP–MLA in a ternary cogrinding system and possessed thermodynamical stability. On the other hand, when grinding with moisture or maintaining at high temperatures and relative humidity conditions, APAP–MLA was more stable, and OXA converted to OXA dihydrate. In the slurry method, APAP–OXA was more stable in aprotic solvents because the APAP–OXA with low-solubility product precipitated.

Conclusions: The relative stability order was affected by preparing conditions of presence of moisture. This order might attribute to the small difference of crystal structure in the extension of the hydrogen bond network.     

Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Abstract

Objective: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.

Significance: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.

Methods: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.

Results: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.

Conclusions: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.     

Stability to moisture for chemically vapour-deposited boron nitride

Chemically vapour-deposited boron nitride (CVD-BN) plates prepared by use of the BCl₃-NH₃-H₂ gas system were investigated as to their stability to moisture. Infrared (IR) spectroscopic measurement, chemical analysis and thermal gravimetric analysis were used in this study. The synthesis conditions of CVD-BN plates have a large influence on their stability to moisture. The stability of CVD-BN plates prepared under a total gas pressure (P _tot) of 10 to 60 torr degraded as the deposition temperature (T _dep) was lowered. The CVD-BN plates with transparent and isotropic properties, which were prepared at below 1400° C and above 10 torr, showed poor stability to moisture, The CVD-BN plates synthesized under 5 torr had high moisture-resistance, even at aT _dep as low as 1400° C. An IR absorption spectral study revealed that the unstable species existing in CVD-BN plans had changed to ammonium borate hydrates by reacting with moisture in the atmosphere. The stability to moisture for CVD-BN plates degraded as the deposition roe was raked, especially for the CVD-BN plates prepared at 1400° C.     

The Effect of Moisture Sorption and Desorption on Furosemide Tablet Properties

Abstract

The effect of moisture sorption and desorption on the physical characteristics of furosemide tablet was studied at moderately elevated temperatures and different relative humidity conditions over 20 days. The rate of moisture sorption and desorption was founud to follow first order kifietics within first hours. Except ambient conditions (RT/Amb.RH), moisture sorption caused a decrease in hardness values of furosemide tablets. Also the disintegration times of hydrated tablets showed a remarkeable decrease. Changes in hardness and disintegration time were dependent on the amount of water sorbed into the tablets. These significant changes occured during the first days of the test and then became invariant. The variations in hardness and disintegration times of tablets were irreversible as demonstrated by desorption experiments.

Furthermore, except storage at high temperature and high relative humidity dissolution parameters of tablets were less affected by moisture sorption and desorption.     

Controlled Release by Permeability Alteration of Cationic Ammonio Methacrylate Copolymers Using Ionic Interactions

Abstract

A multiparticulate drug delivery system was studied in which the drug release of a model drug theophylline could be modulated by interactions of ammonio methacrylate polymer and anions. The system consisted of a EUDRAGIT® NE coated anionic core, layered with drug and further layered with EUDRAGIT® RS. The effects of different anions like chloride, succinate, citrate, and acetate as well as the thickness of the polymer layers on the in vitro drug release were studied. It was seen that succinate and acetate anions had permeability enhancing effects and citrate and chloride anions had permeability retarding effects on the polymer. The results indicate that changing these variables would enable us to get a desired release profile and hence the proposed system could be a viable alternative to existing technologies for the development of a controlled drug delivery system.     

Development of chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis

The aim of this research was to develop chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis, which was fabricated through an environmental friendly process. Mucoadhesive films increase the advantage of higher efficiency and drug localization in the affected region. In this research, mucoadhesive films, for the release of hydrocortisone sodium succinate, were prepared using different ratios of chitosan, gelatin and keratin. In the first step, chitosan and gelatin proportions were optimized after evaluating the mechanical properties, swelling capacity, water uptake, stability, and biodegradation of the films. Then, keratin was added at different percentages to the optimum composite of chitosan and gelatin together with the drug. The results of surface pH showed that none of the samples were harmful to the buccal cavity. FTIR analysis confirmed the influence of keratin on the structure of the composite. The presence of a higher amount of keratin in the composite films resulted in high mechanical, mucoadhesive properties and stability, low water uptake and biodegradation in phosphate buffer saline (pH?=?7.4) containing 10⁴?U/ml lysozyme. The release profile of the films ascertained that keratin is a rate controller in the release of the hydrocortisone sodium succinate. Finally, chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate can be employed in dental applications.     

Aging of Tablets Prepared by Direct Compression of Bases with Different Moisture Content

Abstract

Properties of aged tablets prepared by the wet granulation method were found to be affected by the moisture content of the granules. In this study, the storage-induced changes in hardness, disintegration and drug release were evaluated for tablets made by direct compression of three different bases with different initial moisture content. Tablets with high initial moisture content were found to increase in hardness upon storage. The magnititude of such increase is dependant upon the physical properties of the base and the absolute moisture content. The increase in hardness may increase the disintegration time and decrease drug release. Tablets with low initial moisture content were minimally affected by storage. The gain of moisture by some of these tablets led to enhancement in disintegration and drug release. Among the tablets studied lactose based tablets with different initial moisture content were found to be the most resistant to changes upon storage.     

Effect of Moisture on the Physical and Chemical Stability of Granulations and Tablets of the Angiotensin Converting Enzyme Inhibitor,Enalapril Maleate

Abstract

Granulations and tablets of enalapril maleate in a lactose matrix were stored in open petri dishes at a range of relative humidities and respective moisture uptakes measured, Extrapolation of the moisture uptake rates measured at the exaggerated humidities yielded a critical humidity, i.e. humidity where the moisture uptake rate is zero and, therefore, least detrimental to the product.

Enalapril maleate was reasonably stable at the storage conditions. The hardness of the tablets decreased at all humidities except when stored with silica-gel. The disintegration times were unaffected except at very high humidities. The dissolution profiles of the tablets remained unchanged.     

Effect of Moisture Content on Compression Properties of Directly Compressible High Beta-Content Anhydrous Lactose

Abstract

Moisture sorption characteristics and the role of moisture on the compression properties of direct compression anhydrous lactose was investigated. Anhydrous lactose sorbed little moisture even when exposed to very high relative humidities. The equilibrium moisture content of the diluent was less than 1% at 55% relative humidity, 1.66% at 80% relative humidity and 2.03% at 92% relative humidity. An increase in moisture content of lactose resulted in a reduction in hardness of the tablets and increased pressure requirements to achieve specified hardness values. Heckel plots obtained from the compression data of the diluent were linear for all moisture contents. Yield pressures calculated from the Heckel plots increased at moisture contents greater than that of the original diluent. Differential scanning calorimetry performed on the diluent with 5.13% moisture showed that the added water was bound as the crystalline hydrate.