Pure Active Substance Research Articles

Detection of organophosphorus pesticides in dairy products by thin layer chromatography

The aim of the research was to determine the residual amounts of organophosphorus pesticides in milk, after treatment of the skin of cattle, using the method of thin layer chromatography. The studies were carried out on the basis of the Department of Veterinary and Sanitary Expertise of the St. Petersburg State University of Medicine. The material was milk samples taken 7 days and 14 days and 21 days after treatment of the animals. In parallel, control samples containing pure active substance were applied to chromatographic plates. Results were evaluated under UV light using a UVC-HDi UV cabinet. Based on the results of the studies, the dependence and sensitivity of the method to the detection of pesticides in milk after treatment of animals with diazinon-C was established. The size of the spots of the applied samples on day 7 after treatment was less than on day 14, and on day 21, the substance was not detected in the samples. Thus, this method can establish not only the presence of microconcentrations of substances in the samples, but also the dependence of their number on the size of spots on the chromatographic plate.

PREPARATION AND IN VITRO CHARACTERIZATION OF VANCOMYCIN LOADED PLGA NANOPARTICLES FOR THE TREATMENT OF ENTEROCOCCUS FAECALIS INFECTIONS

Objective: In this study, it was aimed to prepare Vancomycin loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles that can be used parenterally in enterococcal infections. Material and Method: In the study, different concentrations of PLGA were used to prepare nanoparticles. Emulsification-solvent evaporation method was used in the preparation of the particles. Particle size and distribution, zeta potential, encapsulation efficiency and yield of the prepared formulations were determined. FTIR analyses were also performed for the formulations. The antibacterial activity was determined as a minimum inhibition concentration by broth microdilution method and as an inhibition zone by disk diffusion method against Enterococcus faecalis ATCC 29212 according to European Committee on Antimicrobial Susceptibility Testing and its effectiveness on bacteria was interpreted by comparing with the pure active substance. Result and Discussion: Particles were successfully prepared by emulsion-solvent evaporation method. Around 300 nm; Particles with a high amount of encapsulated Vancomycin were obtained at PDI values of 0.26-0.28. As a result of the FTIR analysis, it was determined that Vancomycin was loaded into the particle. The MIC values of the prepared PLGA nanoparticles against Enterococcus faecalis ATCC 29212 strain was found to be 4 µg/ml, and the inhibition zone diameters were measured as 15 mm, 15 mm and 16 mm, respectively.

No needle mesotherapy device in treatment of corticosteroid induced striae in systemic lupus erythematosus patients.

Introduction: is a needle free mesotheraputic device that is able to insert analytical pure active substance to the deep layers of skin within cell levels using the most modern electroporation procedure. Objectives: this study aimed to assess electroporation as a method of transdermal administration of medications in treatment of corticosteroid induced striae in systemic lupus erythematosus patients. Methods: Twenty female Systemic lupus erythematous (SLE) patients suffering from corticosteroid induced striae in different body parts, were included in this study. Patients were subjected to full history taking, complete clinical examination, and assessment of disease activity using systemic lupus erythematosus disease activity index (SLEDAI) score. Each patient received treatment in the form of six weekly successive cessions using electroporation device Mesostyle and photos were obtained after each cession. Results: We found marked improvement of striae appearance with noticeable patients’ satisfaction without any adverse effects. Conclusion: This study supports the role of electroporation which is safe, tolerable, non-invasive, and effective method for transdermal administration of medications.

Ispitivanje reološkog ponašanja i njegov značaj za procenu aplikativnih svojstava i fizičke stabilnosti hidrogelova sa fitosomima

Phytosomes are amphiphilic molecular complexes of substances of plant origin and phospholipids that are considered as active ingredients of dermopharmaceutical and cosmetic formulations of potentially improved efficiency. The study aim was the formulation of carbomer hydrogels with commercially available phytosomes of escin (Escin ß-Sitosterol Phytosome®) (EP) and 18-ß glycyrrhetinic acid (18-ß Glycyrrhetinic Acid Phytosome®) (GP) and evaluation of their application properties and real-time physical stability. Phytosomes incorporation did not significantly affect pH of the hydrogels, which was acceptable for cutaneous application. However, these hydrogels had significantly different organoleptic properties (opaque and softer consistency) compared to the hydrogel without active substance (C) and the hydrogels with pure active substances (E and G) used for comparison. The values of maximum and minimum apparent viscosity and yield stress were significantly lower in phytosome-loaded hydrogels. The results of oscillatory rheological analysis indicated that viscous character prevails in EP and GP hydrogels (elastic modulus (G')˂viscous modulus (G")), while in hydrogels C, E and G elastic properties were more pronounced (G'˃G"). Escin phytosome had greater influence on carbomer gel network strength. Phytosome-loaded hydrogels were physically stable during 24 months of storage under ambient conditions, although the rheological analysis also indicated a potential risk of sedimentation.

Impact of chronic exposure of rainbow trout, Oncorhynchus mykiss, to low doses of glyphosate or glyphosate-based herbicides

Glyphosate is an herbicidal active substance (AS) entering in the composition of a large diversity of pesticide products (glyphosate-based herbicides; GBH) used in modern intensive agriculture. This compound has a favorable environmental safety profile but was suspected to induce deleterious effects in aquatic organisms, with a potential effect of some associated co-formulants. This study aimed to assess the impact of direct and chronic exposure to glyphosate on the health status of rainbow trout, Oncorhynchus mykiss. A total of 36 genitors were exposed daily for 10 months to a dose of glyphosate representative of environmental concentrations (around 1 μg L−1) using the AS alone or two GBHs formulations (i.e. Roundup Innovert® and Viaglif Jardin®) and findings were compared to an unexposed control group (n=12). The effects of chemical exposure on the reproductive capacities, hemato-immunologic functions, energetic metabolism, oxidative stress and specific biomarkers of exposure were analyzed over a period of 4 months covering spawning. A limited mortality between 15% and 30% specific to the spawning occurred under all conditions. No differences were observed in reproduction parameters i.e. mean weights, relative fertility and fecundity. Red blood cell count, hematocrit index, mean corpuscular volume and white blood cell counts were similar for all the sampling dates. Significant changes were observed two months before spawning with a 70% decrease of the proportion of macrophages in trout exposed to Viaglif only and a reduction of 35% of the phagocytic activity in fish exposed to the two GBHs. Trends towards lower levels of expression of tumor necrosis factor-α (between 38% and 66%) were detected one month after the spawning for all contaminated conditions but without being statistically significant. Biomarkers of exposure, i.e. acetylcholine esterase and carbonic anhydrase activities, were not impacted and none of the chemical contaminants disturbed the oxidative stress or metabolism parameters measured. These results suggest that a 10 months exposure of rainbow trout to a concentration of 1 μg L−1 of glyphosate administered using the pure active substance or two GBHs did not significantly modify their global health including during the spawning period. The immunological disturbances observed will need to be further explored because they could have a major impact in response to infectious stress.

A Study on the Behavior of a Polyurethane Drug Carrier in Various pH Media.

Polyurethane nano- and micro-structures have been studied intensively in the last decade as drug delivery systems for various herbal extracts as well as pure active biological substances. Their biocompatibility, haemocompatibility, safe degradation, and low-cost production are just a few advantages of these materials that were already used in numerous medical applications (catheters, surgical drapes, wound dressing). The primary purposes of this study include obtaining empty polyurethane microstructures and the assessment of their modifications in media with different pH values. A mixture of two aliphatic diisocyanates and an aqueous phase based on a polyether were used during the synthesis process. The size, homogeneity, and surface charge were studied using a Cordouan Technol. Zetasizer, while the pH measurements were conducted with a portable pH Meter Checker®, Hanna Instruments. The results showed the obtaining of an almost homogeneous sample containing microstructures with sizes ranging between 139 and 151 nm, with a pH value of approximately 6.78 and a Zeta potential of 24.6. Expected decreases in microparticles’ sizes were observed in all types of media during a 15-days experiment, but the process was accelerated by a low pH when an increase of the Zeta potential value was noticed as well. Our data provide new information about the degradation process of the polyurethane microstructures on the one hand and the drug release rate of these materials when used as drug carriers, on the other hand.

Application of combined solid-state NMR and DFT calculations for the study of piracetam polymorphism

Piracetam, a popular nootropic drug, widely used in the treatment of age-associated mental decline and disorders of the nervous system such as Alzheimer's disease and dementia exists under normal pressure in three polymorphic forms (P1, P2 and P3) of different stability. In this work the relative stability of piracetam polymorphs depending on the temperature was studied using the ssNMR spectroscopy combined with ab initio DFT calculations. The ssNMR spectroscopy enabled the analysis of polymorphic phase transition in the case of pure active substance as well as polymorphic form identification in the analysis of the commercial solid dosage formulations. Quantum chemical calculations of phonon density of states were performed to obtain the temperature dependence of the enthalpy, entropy and free energy of the piracetam polymorphs in a quasi-harmonic approximation. GIPAW NMR calculations combined with molecular dynamics were performed to support the chemical shift assignment. The obtained results showed that DFT calculations can be used not only to obtain the NMR parameters but also to predict the influence of the temperature on the stability order of the polymorphic forms of molecular crystals.

Commercial phenoxyacetic herbicides control heavy metal uptake by wheat in a divergent way than pure active substances alone

BackgroundImpact of two widely used commercial herbicides, i.e. Aminopielik D 450 SL and Chwastox 300 SL, on the uptake and translocation of selected heavy metals in wheat plants Triticum aestivum L. cultivated in the laboratory pot experiments was investigated. Mineral-humus, loamy sand soil representative for the central part of Poland was applied. Bioavailable, exchangeable and total forms of Cd, Co, Cu, Zn, Pb, and Mn were determined. Transfer coefficients, translocation, and bioaccumulation factors illustrating metal migration in the plant were investigated.ResultsAdministration of commercial herbicides significantly altered heavy metals uptake by wheat in a way distinctively different than that observed for the parent chemically pure synthetic auxins, i.e. 2,4-D and MCPA. In particular, Aminopielik D 450 SL and Chwastox 300 SL prompted heavy metals accumulation in roots as indicated by their high transfer coefficients. Further transport to above ground part of the plant was limited and element dependent.ConclusionsThis work clearly shows that commercial herbicide formulations may act in a distinctively different way than pure active ingredients alone.

Sol-gel synthesis of anatase nanopowders for efficient photocatalytic degradation of herbicide Clomazone in aqueous media

TiO2 nanopowders were produced by sol-gel technique using TiCl4 as a starting material. For the preparation of crystalline anatase with developed surface area, this aqueous solution has been mixed with 0.05 M or 0.07 M (NH4)2SO4 solution in a temperature-controlled bath. The pH values of the suspension were 7, 8 or 9. According to the x-ray diffraction (XRD) analysis the anatase crystallite sizes were about 12 nm, which coincided with the average particle size revealed by scanning electron microscopy (SEM). The Raman scattering measurements have shown the presence of a small amount of highly disordered brookite phase in addition to dominant anatase phase with similar nanostructure in all synthesized powders. BET measurements revealed that all synthesized catalysts were fully mesoporous, except the sample synthesized with 0.07 M (NH4)2SO4 at pH=9, which had small amount of micropores. The photocatalytic degradation of herbicide Clomazone was carried out for both the pure active substance and as the commercial product (GAMIT 4-EC) under UV irradiation. The best photocatalytic efficiency was obtained for the catalyst with the largest specific surface area, confirming this parameter as crucial for enhanced photocatalytic degradation of the pure active substance and commercial product of herbicide Clomazone.

Biological activities associated to the chemodiversity of the brown algae belonging to genus Lobophora (Dictyotales, Phaeophyceae)

Although Lobophora belongs to a marine algal family (Dictyotaceae) that produces a large array of secondary metabolites, it has received little attention compared to other genera, such as Dictyota, in terms of natural compounds isolation and characterization. However, metabolites produced by Lobophora species have been found to exhibit a wide array of bioactivities including pharmacological (e.g. antibacterial, antiviral, antioxidant, antitumoral), pesticidal, and ecological. This review aims to report the state-of-the-art of the natural products isolated from Lobophora species (Dictyotales, Phaeophyceae) and their associated bioactivities. All bioactivities documented in the literature are reported, therefore including studies for which pure active substances were described, as well as studies limited to extracts or fractions. From the early 1980s until today, 49 scientific works have been published on Lobophora chemistry and bioactivity, among which 40 have reported bioactivities. Only six studies, however, have identified, characterized and tested no less than 23 bioactive pure compounds (three C21 polyunsaturated alcohols, three fatty-acids, a macrolactone, 11 polyketides, a few sulfated polysaccharides, three sulfolipids, a tocopherol derivative). The present review intends to raise awareness of chemists and biologists given the recent significant taxonomic progress of this brown algal genus, which holds a promising plethora of natural products yet to be discovered with ecological and pharmacological properties.

A levodopa dry powder inhaler for the treatment of Parkinson’s disease patients in off periods

Adequate treatment of Parkinson’s patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronization, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterized in vitro over a range of pressure drops (2–6kPa) and doses (20, 30 and 40mg), representative of those to be expected in practice. A co-micronized levodopa formulation with 2% l-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson’s patients in an off period.

Kinetic analysis of solid-state degradation of pure pravastatin versus pharmaceutical formulation

In this paper, the kinetic behavior of decomposition of a well-known bioactive substance used for treating dyslipidemia and the prevention of cardiovascular disease drug from statin class, namely pravastatin, was described. The kinetic study was performed on the main decomposition process which occurs at nearly 200 °C, for both pure active substance and a generic commercial formulation that contain 40 mg pravastatin per tablet, using Kissinger, Friedman, Kissinger–Akahira–Sunose, Flynn–Wall–Ozawa and NPK methods. The stability of pravastatin as pure active substance and as tablet was compared by means of kinetic data, and the results suggested that in the solid pharmaceutical formulation, PRV has an increased stability compared to pure active substance.

Development and validation of stability indicating chromatographic method for determination of impurities in maprotiline pharmaceutical tablets

A simple, sensitive and accurate HPLC method has been developed and validated for determination impurities in maprotiline solid dosage forms. Chromatographic separation was achieved on Lichrospher RP Select B column (250 mm × 4.6 mm i.d., particle size 5 μm, maintained at 40°C) by a mobile phase consisted of ammonium hydrogen carbonate (pH 8.1; 0.05 M)-acetonitrile-methanol-tetrahydrofuran (20: 80: 32: 4.5, v/v/v/v) and a flow rate of 1.0 mL/min. The detection wavelength was set at 215 nm and injection volume was 10 μL. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The degradation products, when any, were well resolved from the pure active substance with significantly different retention time values, thus proved the stability indicating power of the method. The method met the International Conference on Harmonisation (ICH) regulatory requirements. The results demonstrated that the method would have a great value when applied in quality control and stability studies for maprotiline tablets.

Why do we have for health claims different criteria between plant based food supplements and herbal medicinal products?

It seems obvious for most of the people that there are strong differences between botanical food supplements and herbal medicinal products, especially because consumers as well as treatment goals are not the same. However, some main convergences can be observed as for example quality and safety. A key question today is why for a given plant and the same preparation, the requirements imposed by the official European authorities (EMEA) are less severe in terms of clinical assessments to get a marketing authorization for a food product in comparison to a medicinal product? In the EU, traditional herbal medicinal products having a long history of prior human usage can be registered under a special, simplified registration procedure without the necessity of providing some proofs of efficacy with clinical trials. This is the consequence of a specific legal framework known as Directive 2004/24/EC. On the contrary, regarding food products, EFSA requires randomized clinical trials on healthy subjects and under such requirements no “traditional claims” will obtain a positive opinion from this Authority. Furthermore, it is really difficult to understand that for a drug, designed for a targeted disease and focused on a given pharmacological activity, the proof of its efficacy is not required in a contrary to a food supplement, used to maintain the homeostasis status and to help in minor troubles, where the efficacy proof is required. The dosage of a plant extract being lower for a food supplement than for a drug reinforces the difficulty to get the validation. How can we demonstrate such efficacy on a person without evident pathology but having only some well-being problems? In a scientific perspective, this clinical approach is adapted to pure active substances as vitamins but not to the complexity of plant extracts. Many years ago, a group of experts at the Council of Europe proposed some recommendations to differentiate the requirements necessary for food supplements and for herbal drug medicine, taking into consideration for example the individual impact and the final aim of the product. Unfortunately, this proposal has not been retained. In conclusion, we consider today that the requirements necessary to get a validated health claim for botanical food supplements and botanical preparations are not appropriate, leading to an insoluble situation. European harmonization is more and more necessary.

Computer simulation of negative electrode operation in lithium—ion battery: Galvanostatic discharge, porous electrode model and film model

Computer simulation of the structure and methods of operation (galvanostatic discharge) of the negative electrode of a lithium-ion battery is performed. Two possible models of the active anode layer were compared. 1. The model of porous active layer (mixture of active substance grains with grains of electrolyte). Here, the electrochemical process occurs within a porous active layer. 2. The film model (constant-thickness layer) of pure active substance (intercalating agent) grains without admixture of grains of electrolyte. In this case, the electrochemical reaction occurs only on the planar active electrode layer/interelectrode space interface. In both cases, the optimum working parameters of anode active layers were calculated: porous active layer thickness (in the film model, this was the calculation parameter), duration of full anode discharge, specific electric capacitance and finite difference between the intercalating agent/electrolyte potentials at the active anode layer/interelectrode space interface. It is found that each of these two models has its advantages and faults. Specific electric capacitance C cannot exceed the values of the order of magnitude of 10 C/cm2 when a porous active layer is used. Whereas in the film model, much higher values of C may be obtained: tens and even hundreds of C/cm2. On the other hand, in the case of anode discharge, the reasonable discharge current density value, its maximum value, at which practically full recovery of lithium atoms from active intercalating agent grains is still possible, proves to be by orders of magnitude higher in the case of an anode with a porous active layer, as compared with a film-type anode. Thus, in the case of development of electrode active layers of lithium-ion batteries, there is a possibility of choosing from two variants. There is the variant of an active film-type layer providing high capacitance values, but low discharge current density. Or there is another variant: a porous active layer with limited capacitance but then much higher values of discharge current density.

EN

Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oral-inhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure active substances were more severe than those derived from dermal data in more than 98% of cases, which calls into question the value of routine dermal route testing for acute toxicity. Oral classifications were equivalent to or more severe than for the inhalation route for 83% of industrial chemicals and for 48% of pesticides examined.

Busulfan systemic exposure after oral administration of extemporeanously prepared high-dose busulfan capsules

The aim of the study was to analyze patients' busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation. Patients were treated with 1 mg/kg body weight BU administered orally every 6h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detection. In addition, in two patients concomitant TDM was executed. BU exposure was monitored concurrently and BU doses were targeted to achieve a steady-state plasma concentration (C(SS)) of 600-900 ng/mL or 900-1100 ng/mL depending on the underlying disease. In these patients blood samples were obtained 0, 60, 120, 180, 240, and 360 min after the 1st, 5th, 9th, and 13th BU dose and analyzed concurrently. For the six patients monitored retrospectively, the time to reach peak plasma BU concentration (C(max)) ranged from 1 to 5 h (mean 2.4 h). BU C(max) - values varied from 728 to 1807 ng/ mL (mean 1174 ng/mL), and BU clearance (CL/F) from 2.32 to 3.75 mL/min/kg (mean 2.97 mL/min/ kg). The mean BU steady state (C(SS)) concentration calculated was 973 ng/mL (range 754-1226 ng/mL) with a mean AUC of 5818 ng.h/mL (range 4521- 7171 ng.h/mL). One of the two patients receiving targeted BU doses required an upward dose adjustment. None of the eight patients suffered from vomiting during BU therapy. BU active substance encapsulated without further excipients in gelatine capsules is highly suitable for oral BU therapy. However, therapeutic drug monitoring and BU dose adjustment is still advisable to achieve optimal systemic BU exposure in each individual patient.

The investigation of new forms of resistance to some antibiotics in E coli strains isolated from piglets

The resistance of bacteria poses a significant problem everywhere in the world, and consequently in our country as well. The non-critical use of antibacterial medicines in human and veterinary medicine has contributed to the spreading of this resistance. Due to the topical importance of this problem, large numbers of states in the world are financing projects of which the objective is to follow and monitor bacterial resistance. The objective of this investigation was to isolate and identify pathogenic strains of E. coli from piglets with clinically manifest diarrhea and to examine the sensitivity of the isolated strains to a certain number of selected antibiotics. The material for these investigations were parts of intestines (jejunum, ileum) from piglets that died, rectal smears and feces of diseased piglets sampled pig farms in the vicinity of Belgrade. Conventional methods of microbiological diagnostics were used for isolation, and conventional and commercial tests API 20E (bio Merieux, France) were used for identification. Following biochemical identification using hyper immune serums for certain group (O) antigens: (O8, O138, O139, O147, O149, and O157), the serological typization of the strains was carried out. Commercial antiserums: T K88 (F4), K99 (F5), and 987P (F6), Toxigenic E. coli pili antisera, Denka Seiken Co. Ltd. Tokyo, Japan) were used to establish the presence and to identify fimbrial antigens-adhesions through slide agglutination reaction. The sensitivity of the antibiotics to the isolated strains of E. coli was examined using the disc diffusion method according to Kirby Bauer and the microdillution method in bouillon according to CLSI recommendations (2008). Examinations using the microdillution method in bouillon were performed with pure active antibiotic substances: ampicillin, apramycin, gentamicin, kanamycin, tetracycline, ceftriaxone, and ciprofloxacin (Sigma, USA). A total of 400 E. coli strains were isolated, including 48 E. coli strains that are within the category of pathogenic strains. Out of the total number of pathogenic strains of E. coli, 32 (66.67%) were found to be multi resistant to 3 or more than 3 antibiotics, and 16 (33.33%) pathogenic strains of E. coli were resistant to 2 or 1 of the examined antibiotics. Resistance to tetracycline and ampicillin was established in 89.58% isolated strains of E. coli, and to ciprofloxacin in 37.5% strains. The lowest percentage of resistance to ceftriaxone was established in 4.17% strains of E. coli. The isolated strains of E. coli were also found to be resistant to certain amino glycosides antibiotics. Thus, resistance to apramycin was established in 18.75% strains whose MIC values were higher than 128 ?g/mL. Resistance to kanamycin was established in 52.08% strains of E. coli, and in these, 96.00% strains showed MIC kanamycin values of over 256?g/mL. Resistance to the third amino glycosides antibiotic, gentamicin, was established in 33.33% E. coli strains. All the E. coli strains that led to diarrhea in piglets were resistant to at least two antibiotics, and more than 50% strains were found to be resistant to more than 3 antibiotics. It is significant to stress that all isolated strains of E. coli covered by these investigations were sensitive only to amikacyn. .

The formulation effect of propoxur on leaching as a function of soil properties

This work investigates the kinetics of propoxur washing out and its residues in five arable soils with a clay content from 4–28% and an organic matter content from 1.3–1.8%. It has been noted that the fastest washing out occured with the emulsion form, the slowest washing out with the pure active substance, whereas an intermediate velocity was observed for the suspension form. The amount of propoxur in the reflux was also highest for the emulsion form, intermediate for the suspension form and lowest for the pure active substance. The highest residue level in the investigated soils was observed for the pure active substance. The kinetics of propoxur washing out in all the investigated forms was inversely proportional to the content of clay particles in the soils. Adsorption increased with the increase of clay particle content.

Preformulation the Role of Moisture in Solid Dosage Forms

Moisture plays an important role in the individual stages of preformulation studies for solid dosage forms. Examples are given to demonstrate thisThe first stage involves chemical tests with the pure active substance using a reliable storage scheme. Then compatibility testing between active and inactive substances is performed. Under the general heading of sorption tests, the determination of sorption isotherms using special apparatus and their correlation with the physical and chemical changes which occur in the samples are discussed. With the results of these tests it is often possible to influence the sorption properties of the finished dosage form, for example by selection of the excipients and the salt form of the active substance, or by deferring the point of ansorptionFinally, as an example of special tests used in pre-formulation, the development of compound preparations is described and the galenical pre-stages are discussed