Investigations on Compaction Behavior of Kollidon®SR-Based Multi-component Directly Compressed Tablets for Preparation of Controlled Release Diclofenac Sodium.

The physics of tablets mixtures has gained much attention lately. The purpose of this work is to evaluate the compaction properties of Kollidon® SR (KSR) in the presence of different excipients such as Microcrystalline cellulose (MCC), Monohydrous lactose (MH Lactose), Poly (vinyl acetate) (PVA100), and a water-soluble drug Diclofenac sodium (DNa) to prepare once daily formulation. Tablets were prepared using direct compression and were compressed into flat-faced tablets using hydraulic press at various pressures. The combination of MCC and KSR in the tablets showed reduced porosity, and almost constant low Py values as KSR levels increased; also, KSR-DNa tablets had higher percentage porosity and crushing strength values than KSR-MH Lactose tablets. The crushing strengths of KSR-MCC tablets were larger than those of KSR-DNa tablets. Ternary mixture tablets comprised of KSR-MCC-DNa showed decreased porosities and low Py values as the percentage of KSR increased especially at high compression pressures but had higher crushing strengths compared to KSR-DNa or MCC-DNa binary tablets. KSR-MH Lactose-DNa ternary tablets experienced lower porosities and crushing strengths compared to KSR-MCC-DNa tablets. Quaternary tablets of KSR-PVA100-MCC-DNa showed lower porosity and Py values than quaternary tablets obtained using similar proportion of MH Lactose instead of MCC. In conclusion, optimum quaternary tablets were obtained with optimum crushing strengths, relatively low Py, and moderate percentage porosities among all prepared quaternary tablets. The drug release of the optimum quaternary tablets demonstrated similar in vitro release profile compared to that of the marketed product with a mechanism of release that follows Korsmeyer-Peppas model.

Investigating the Correlation Between Drug Physical Properties and Physical Characteristics and Drug Entrapment Efficiencies of Chitosan-TPP Nanoparticles.

Chitosan nanoparticles (NPs) have been the subject of intensive research. This study aimed to determine how different drug characteristics such as molecular weights, drug solubility in the processing medium, and drug ionization/charge state affected chitosan NPs particularly their percentage entrapment efficiency (% EE) and mean hydrodynamic diameters (MHDs). Drugs with varying molecular weights but of similar aqueous solubilities were chosen and were dissolved in a 2% chitosan-acetic acid solution. Chitosan NPs were formed using by ionic gelation technique using sodium tripolyphosphate (TPP) at specific concentration and volume ratios of chitosan to TPP. NPs containing Enalapril and Paracetamol displayed better short-term stability in terms of MHDs. A direct relationship between MHDs of NPs and chitosan concentrations was found. In comparison, at both low and high admixed drug concentrations and at high chitosan concentration, larger NPs sizes were associated with the lower molecular weight drug (Paracetamol). However, the study did not demonstrate a direct relationship between NPs characteristics such as MHDs and drugs molecular weights. The ZP of Paracetamol-loaded NPs was lowest at high drug concentrations at all chitosan concentrations compared to other drugs-loaded NPs. When compared to drugs with high and low molecular weights, medium molecular weight Atenolol showed the highest % EE. This clearly indicated that there was no direct correlation between drug molecular weight and % EE, but rather other factors influenced on % EE. Nevertheless, an inverse linear relationship with high correlation coefficients was only found when % EE was plotted against each drug molecular weight divided by the ratio of drugs solubilities in acetic acid to their employed concentrations, however the correlation was inconsistent between drugs of varying molecular weights.

The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and Drugs Entrapment Efficiencies into Chitosan-TPP Nanoparticles.

Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.

Assessment of Once Daily Controlled-release Ibuprofen Matrix Tablets Prepared using Eudragit ®E100/Carbopol® 971P NF Polymers and their Salt Combinations.

INTRODUCTION: Hydrophilic polymers that swell or dissolve in aqueous media can have the potential to prepare controlled/sustained dosage forms for weakly acidic and poorly soluble drugs. OBJECTIVE: The main objective of this study is to utilize Eudragit®E100 (EE) and Carbopol®971P NF (Cp) polymers and their salt forms for the preparation of a once-daily controlled-release matrix tablet for model drug, Ibuprofen (IB). METHODS: Combinations of the polymers in their base forms (EE)/(Cp) or in their salt forms (EEHCl/ CpNa) were compressed with (IB) into single layer matrix tablets, or otherwise into bilayer tablets. Dissolution profiles were constructed using three different consecutive stages (pH 1.2, 4.8 and 6.8). RESULTS: It was found that the incorporation of (EEHCl) modified the release rates of (IB) from (Cp) based matrix tablets. However, a major enhancement of (IB) release rates occurred when the polymers were combined in their salt forms in a 1:1 ratio by weight. In addition, a bilayer tablet was prepared wherein a relatively rapidly disintegrating layer composed of polymers salts (EEHCl and CpNa), and a second layer containing only (Cp) polymer in its base form in a 1:2 weight ratio possessed excellent release properties and mechanical strength. CONCLUSION: It was concluded that the prepared bilayer tablet could be promising for controlling the release rates of (IB) in an extended manner to allow once-daily administration with an improved pH-independent release behavior.

Preparation and Evaluation of Ternary Polymeric Blends for Controlled Release Matrices Containing Weakly Basic Model Drug.

OBJECTIVE: The objective of this study was to evaluate the suitability of a ternary mixture of smart polymers comprised of Eudragit®E100, Eudragit®L100, and sodium alginate to serve as a carrier for sustained drug release for weakly basic drugs. The model drug chosen in this part of the study is Metronidazole. METHODS: Matrix tablet formulations were prepared by either direct compression or by wet granulation. Dissolution studies were conducted using USP XXΠ rotating paddle apparatus in three different consecutive stages (pH 1.2, 4.8, and 6.8). Tablets made of low to intermediate proportions of sodium alginate and approximately equal proportions of Eudragit®E100 and Eudragit®L100 were found to have a significant modification of drug release rates. RESULTS: Thus, indicating a potential for controlling the drug release for 12 hours depending on polymers ratios in the formulation. The ratio of sodium alginate to total Eudragit® polymers and the ratio of Eudragit®E100 to Eudragit®L100 within the ternary polymeric composition were found critical in determining the controlled release performance. CONCLUSION: Results of swelling studies were in agreement with the dissolution behaviors of the tablets. The findings suggest the significance of the ternary polymeric compositions in controlling the release of a weakly basic drug, Metronidazole.

Withdrawn: Novel Ternary Polymeric Blends for Controlled Release Matrices Containing Weakly Basic Model Drug.

Ahead of Print article withdrawn by publisher.

Development of a Mini-Freeze Dryer for Material-Sparing Laboratory Processing with Representative Product Temperature History.

The goal of the work described in this publication was to evaluate a new, small, material-sparing freeze dryer, denoted as the "mini-freeze dryer or mini-FD", capable of reproducing the product temperature history of larger freeze dryers, thereby facilitating scale-up. The mini-FD wall temperatures can be controlled to mimic loading procedures and dryer process characteristics of larger dryers. The mini-FD is equipped with a tunable diode laser absorption spectroscopy (TDLAS) water vapor mass flow monitor and with other advanced process analytical technology (PAT) sensors. Drying experiments were performed to demonstrate scalability to larger freeze dryers, including the determination of vial heat transfer coefficients, K v . Product temperature histories during K v runs were evaluated and compared with those obtained with a commercial laboratory-scale freeze dryer (LyoStar II) for sucrose and mannitol product formulations. When the mini-FD wall temperature was set at the LyoStar II band temperature (- 20°C) to mimic lab dryer edge vials, edge vial drying in the mini-FD possessed an average K v within 5% of those obtained during drying in the LyoStar II. When the wall temperature of the mini-FD was set equal to the central vial product temperature, edge vials behaved as center vials, possessing a K v value within 5% of those measured in the LyoStar II. During both K v runs and complete product freeze drying runs, the temperature-time profiles for the average edge vials and central vial in the mini-FD agreed well with the average edge and average central vials of the LyoStar II.

Novel Salted Anionic-Cationic Polymethacrylate Polymer Blends for Sustained Release of Acidic and Basic Drugs.

BACKGROUND: Since a unique matrix tablet formulation that independently controls the release of various drug types is in a great demand, the objective of this research was to develop a sustained release matrix tablet as a universal dosage form using a binary mixture of the salt forms of Eudragit polymers rather than their interpolyelectrolyte complexes. METHODS: Tablets were prepared by wet granulation and compressed at different compression forces, depending on drug type. Dissolution tests were conducted using USP XXII rotating paddle apparatus at 50 rpm at 37°C in consecutive pH stages. RESULTS: Tablets containing Ibuprofen (IB) as a model acidic drug and Metronidazole (MD) as a model basic drug showed controlled/sustained release behavior. For IB tablets containing 80% Ibuprofen and 5% (w/w) polymeric combination; the time for 50% of the drug release was about 24 hours compared to 8.5 hours for plain tablets containing 80% IB. In case of MD, the drug release extended to about 7 hours for tablets containing 80% MD and 5% (w/w) polymeric combination, compared to about 1 hour for plain tablets containing 80% MD. In terms of extending the release of medications, the dissolution profiles of the tablets containing polymeric salts forms were found to be statistically superior to tablets prepared by direct compression of the polymers in their powdered base forms, and superior to tablets containing the same polymers granulated using isopropyl alcohol. CONCLUSION: The findings indicated the significance of combining the polymers in their salt forms in controlling the release of various drug types from matrices.

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol.

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.

The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers.

The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.

Multi-drug resistance and reduced susceptibility to ciprofloxacin among Salmonella enterica serovar Typhi isolates from the Middle East and Central Asia.

Typhoid fever is common in developing countries, with an estimated 120 million infections and 700 000 annual deaths, worldwide. Fluoroquinolones have been the treatment of choice for infection with multidrug-resistant (MDR) Salmonella enterica serovar Typhi (S. Typhi). However, alarming reports of fluoroquinolone-resistance and failure of typhoid fever treatment have recently been published. To determine the proportion of S. Typhi isolates with reduced susceptibility to ciprofloxacin (RSC) from six countries in the Middle East and Central Asia, 968 S. Typhi isolates collected between 2002 and 2007 from Egypt, Uzbekistan, Pakistan, Qatar, Jordan and Iraq were tested for antibiotic susceptibility to five antibiotics using the disc-diffusion method. MDR was defined as resistance to amicillin, chloramphenicol and trimethoprim-sulfamethoxazole. The E-test was employed to determine the MIC of ciprofloxacin only. Nalidixic acid resistance was evaluated as a marker for RSC. Interpretations were made according to CLSI guidelines. MDR strains were considerably more prevalent in Iraq (83%) and Pakistan (52%) compared with the other countries studied (13-52%). Nearly all isolates were susceptible (99.7%) to ceftriaxone. RSC was detected in a total of 218 isolates (22%), mostly from Iraq (54/59, 92%), Uzbekistan (98/123, 80%), Qatar (23/43, 54%) and Pakistan (31/65, 47%). Many of these (21%) were also MDR. Use of nalidixic acid resistance as an indicator for RSC was 99% sensitive and 98% specific. This study reinforces the need for routine antimicrobial susceptibility surveillance of enteric fever isolates and close review of current therapeutic policies in the region.

Capacity building of public health laboratories in Afghanistan: challenges and successes (2007-2011).

The continuing state of conflict and the resulting devastation of infrastructure have made Afghanistan exceptionally vulnerable to disease epidemics. The paper reports initiatives by the United States Naval Medical Research Unit No. 3 to promote capacity building in a number of key medical laboratories and enable the Afghans to detect emerging and re-emerging diseases of public health importance. Equipment, supplies and laboratory staff training were critical for disease diagnosis and fulfillment of obligations of the International Health Regulations 2005. Accordingly, many diseases outbreaks were recently identified, including avian and pandemic influenza, febrile illness, watery diarrhoea, jaundice and leishmaniasis. Clinical samples and disease vectors were collected for analysis, and microbial isolates were obtained for further characterization. The expanded range and enhanced accuracy of laboratory procedures have facilitated selected local laboratories to monitor, detect, identify, assess, contain and respond to public health threats. Nevertheless, policies of sustainability and infectious diseases control need continuous support and emphasis.

Evaluation of tadalafil nanosuspensions and their PEG solid dispersion matrices for enhancing its dissolution properties.

The aim of this work was to prepare and evaluate Tadalafil nanosuspensions and their PEG 4000 solid dispersion matrices to enhance its dissolution rate. Nanosuspensions were prepared by precipitation/ultrasonication technique at 5°C where different stabilizers were screened for stabilization. Nanosuspensions were characterized in terms of particle size and charge. Screening process limited suitable stabilizers into structurally related surfactants composed of a mixture of Tween80 and Span80 at 1:1 ratio (in percent, weight/volume) in adjusted alkaline pH (named TDTSp-OH). The surfactant mixture aided the production of nanosuspensions with an average particle size of 193 ± 8 nm and with short-term stability sufficient for further processing. Solid dispersion matrices made of dried Tadalafil nanosuspensions or dried Tadalafil raw powder suspensions and PEG 4000 as a carrier were prepared by direct compression. Drying was performed via dry heat or via freeze dry. Drug release studies showed that, in general, tablet formulations made of freeze-dried product exhibited faster initial release rates than the corresponding tablets made of oven-dried products which could be attributed to possible larger crystal growth and larger crushing strengths of oven-dried formulations. At best, 60% of drug was released from solid dispersion matrices, while more than 90% of drug was released from TDTSp-OH nanosuspension within the first 5 min. In conclusion, Tadalafil nanosuspensions obtained using a mixed surfactant system provided rapid dissolution rates of Tadalafil that can theoretically enhance its bioavailability.

Capacity building of public health laboratories in Afghanistan: challenges and successes [2007-2011]

The continuing state of conflict and the resulting devastation of infrastructure have made Afghanistan exceptionally vulnerable to disease epidemics.The paper reports initiatives by the United States Naval Medical Research Unit No.3 to promote capacity building in a number of key medical laboratories and enable the Afghans to detect emerging and re-emerging diseases of public health importance.Equipment, supplies and laboratory staff training were critical for disease diagnosis and fulfilment of obligations of the International Health Regulations 2005.Accordingly, many diseases outbreaks were recently identified, including avian and pandemic influenza, febrile illness, watery diarrhoea, jaundice and leishmaniasis.Clinical samples and disease vectors were collected for analysis, and microbial isolates were obtained for further characterization.The expanded range and enhanced accuracy of laboratory procedures have facilitated selected local laboratories to monitor, detect, identify, assess, contain and respond to public health threats.Nevertheless, policies of sustainability and infectious diseases control need continuous support and emphasis

إن حالة الصراع المتواصل وما ينجم عنه من تدمير للبنية الأساسية قد جعلت أفغانستان عرضة بشكل كبير لأوبئة الأمراض. وتعمد هذه الورقة إلى عرض ما طرحته الوحدة الثالثة للبحوث الطبية للبحرية الأمريكية من مبادرات لتعزيز بناء القدرات في عدد من المختبرات الطبية الأساسية، ولتمكين الأفغان من اكتشاف الأمراض الناشئة والمنبعثة والتي تمثل أهمية للصحة العمومية. فالمعدات والإمدادات وتدريب العاملين في المختبرات تعد من الأمور الأساسية في تشخيص الأمراض، والوفاء بالالتزامات بموجب اللوائح الصحية الدولية 2005 . ومن ثم فقد تم مؤخرا اكتشاف العديد من فاشيات الأمراض بما فيها أنفلونزا الطيور والأنفلونزا الجائحية، والأمراض الحموية، والإسهال المائي، واليرقان، وداء الليشمانيات. وقد تم تجميع العينات السريرية ونواقل الأمراض بغرض تحليلها. وتم كذلك الحصول على المستفردات الميكروبية للتعرف بشكل أكبر على المزيد من خصائصها. وقد ساعد توسيع نطاق الإجراءات المختبرية وتعزيز دقتها، مختبرات محلية معينة على رصد واكتشاف وتحديد وتقييم واحتواء المخاطر التي تهدد الصحة العمومية ومجابهتها.ومع هذا فإن السياسات الخاصة بالاستدامة ومكافحة الأمراض المعدية بحاجة إلى مواصلة الدعم والتأكيد

La persistance du conflit ainsi que la destruction des infrastructures qui en résulte ont rendu l'Afghanistan exceptionnellement vulnérable aux épidémies.Le présent travail de recherche détaille les initiatives de l'Unité de recherche médicale de la marine des Etats-Unis d'Amérique [NAMRU-3]visant à promouvoir le renforcement des capacités de plusieurs laboratoires médicaux clés et à permettre aux Afghans de dépister des maladies émergentes et réémergentes qui sont importantes sur le plan de la santé publique.Les équipements, les fournitures et la formation du personnel de laboratoire étaient critiques pour le diagnostic des maladies et le respect des obligations découlant du Règlement sanitaire international [2005]. En conséquence, de nombreuses flambées épidémiques ont récemment été identifiées, notamment les grippes aviaire et pandémique, les maladies fébriles, les diarrhées aqueuses, l'ictère et la leishmaniose.Des échantillons cliniques ainsi que des vecteurs de maladie ont été collectés pour analyse, et des isolats microbiens ont été obtenus pour affiner la caractérisation.L'éventail élargi et la précision accrue des procédures de laboratoire ont permis aux laboratoires locaux sélectionnés de suivre, de dépister, d'identifier, d'évaluer, d'endiguer les menaces de santé publique et d'y répondre.Toutefois, les politiques visant à assurer la pérennité de ces capacités et la lutte contre les maladies infectieuses nécessitent un appui et un effort permanents

[Corneal chrysiasis. Gold salt deposits in the cornea in a patient with rheumatoid arthritis. An analysis with confocal microscopy]. / Crisiasis corneal. Depósitos corneales de sales de oro en paciente con artritis reumatoide. Análisis con microscopía confocal.

CASE REPORT: A 60-year-old woman with rheumatoid arthritis of 20 years onset, on treatment with monthly intramuscular gold salts (GS) for the last 7 years. She complained of suffering from halo vision, and the examination showed a visual acuity of 0.6 in both eyes (BE). The slit lamp showed some deposits in the stroma with scattered golden granulated, without any further inflammatory reaction. DISCUSSION: GS deposits are dose-dependent and reversible, although very slowly. In this article, we introduce, for the first time, evidence of deposits of GS in all layers of the cornea, predominantly in the corneal stroma and in the endothelium.

Crisiasis corneal. Depósitos corneales de sales de oro en paciente con artritis reumatoide. Análisis con microscopía confocal / Corneal chrysiasis. Gold salt deposits in the cornea in a patient with rheumatoid arthritis. An analysis with confocal microscopy

Caso clínico: Mujer de 60 años de edad con artritis reumatoide de veinte años de evolución, en tratamiento con sales de oro (SO) intramusculares mensuales en los últimos 7 años. Refería visión de halos y presentaba una agudeza visual de 0,6 en ambos ojos (AO) y en la lámpara de hendidura destacaban depósitos en el estroma central de AO de material granulado dorado disperso y sin reacción inflamatoria. Se realizó estudio con microscopía confocal. Discusión: Los depósitos de SO son dosis-dependientes y reversibles aunque de forma muy lenta. En este trabajo se presenta por primera vez la evidencia de los depósitos de SO en todas las capas de la córnea, de predominio en el estroma y endotelio corneales (AU)

Case report: A 60-year-old woman with rheumatoid arthritis of 20 years onset, on treatment with monthly intramuscular gold salts (GS) for the last 7 years. She complained of suffering from halo vision, and the examination showed a visual acuity of 0.6 in both eyes (BE). The slit lamp showed some deposits in the stroma with scattered golden granulated, without any further inflammatory reaction. Discussion: GS deposits are dose-dependent and reversible, although very slowly. In this article, we introduce, for the first time, evidence of deposits of GS in all layers of the cornea, predominantly in the corneal stroma and in the endothelium (AU)

Comparative analysis of Shigella sonnei biotype g isolated from paediatric populations in Egypt, 1999-2005.

Strain characteristics of 51 Shigella sonnei isolates obtained from children seeking medical care (MC) and 48 isolates recovered during a prospective diarrhoea birth cohort (BC) study were compared. Biochemical characterization and antibiotic susceptibility testing determined that all S. sonnei isolates were biotype g and multidrug-resistant. Plasmid profiling identified 15 closely related patterns and XbaI pulsed-field gel electrophoresis confirmed the high degree of genetic similarity between isolates. All S. sonnei isolates harboured ipaH and class II integrase genes and 84∙3 and 80% of the MC and BC isolates, respectively carried the sen gene. Neither the class I integrase nor the set gene was detected. Our results indicate that S. sonnei isolates associated with severe diarrhoea were indistinguishable from those associated with mild diarrhoea. Additional genetic tests with greater discrimination might offer an opportunity to determine genetic differences within the globally disseminating biotype g clone.

Evaluation of hydrophilic matrix tablets based on Carbopol(®) 971P and low-viscosity sodium alginate for pH-independent controlled drug release.

BACKGROUND: The aim of this study was to evaluate matrix tablets containing different ratios of Carbopol(®) 971P (CP) to low-viscosity sodium alginate (SA) and assess their suitability for pH-independent controlled drug release. METHODS: Two processing methods (physical mixing, PM and spray-drying, SD) were applied before compaction and the release from corresponding matrices was compared. The release from CP-SA PM matrices was also investigated using three model drugs (paracetamol, salicylic acid, and verapamil HCl) and two dissolution media (0.1 N HCl or phosphate buffer, pH = 6.8), and the release rate, mechanism, and pH-dependence were characterized by fitting of Higuchi and Peppas models, and evaluation of similarity factor. Furthermore, swelling behavior of CP-SA matrix tablets was studied for evaluating its impact on drug release. RESULTS: The processing method (SD or PM) markedly affected the drug release from CP-SA matrices. ANOVA tests showed significant effects of the CP:SA ratio and drug type on the release rate (expressed by the constant, K(H), from Higuchi model) and of the dissolution medium on the release mechanism (expressed by the exponent, n, from Peppas model). Similarity factor (f2) indicated that the CP:SA ratios ≥ 25:75 and ≥ 50:50 were suitable for pH-independent release of paracetamol and salicylic acid, respectively, although for verapamil HCl, the matrix with low CP:SA ratio (0:100) showed remarkably reduced pH-dependence of release. Swelling parameters (water uptake and mass loss) were significantly changed with experimental variables (CP:SA ratio, medium, and time) and were in good correlation with drug release. CONCLUSION: Matrix tablets based on CP and SA form a potentially useful versatile system for pH-independent controlled drug release.

Preservation of nanostructured lipid carriers (NLC).

Due to their positive features (e.g., increased penetration of actives, re-enforcement of the lipid barrier and increase in skin hydration), nanostructured lipid carriers (NLC) are used in many dermal formulations. These formulations require preservation, and preservatives can impair the physical stability of disperse systems. Therefore, in this study, the influence of preservatives on the physical stability of Q10-loaded NLC was investigated using 11 different preservative mixtures. Whereas for nanosuspensions, only a limited number of preservatives are known from the literature not affecting their physical stability, a surprisingly high number of seven preservatives could be identified to be suitable for the preservation of NLC dispersions. For Q10-loaded NLC, Hydrolite 5 proved to be the best preservative, as it was found surprisingly to stabilize the NLC dispersion. Based on the data, a preservative classification system is suggested and a mechanistic model describing six key parameters affecting the physical stability of NLC could be developed. As most suitable characterization method to screen for suitable preservatives, light microscopy was identified. By being a simple, fast and cost efficient method, even extensive preservative screening studies can be performed very efficiently.