Abstract: Hydrophilic polymers using as matrix former in matrix tablets is a common approach and well-known excipient Carbopol is widely used for this reason too. In common case polymer doesn’t interact with drug but Carbopol is weak polyacrylic acid and obvious can interact at physiological enteric conditions with weak base drugs like trimetazidine dihydrochloride. During matrix tablet dissolution at enteric conditions the microenvironment pH inside tablet changed from surface to center. Was found that hydrated matrix has unusual structured in microenvironment pH diapason of possible trimetazidine-Carbopol interaction. This matrix structuration resulted in significant matrix behavior changing and increasing trimetazidine release retardation in comparison with release data at gastric conditions. Thus the example of trimetazidine-Carbopol interaction demonstrates additional mechanism of drug retardation that could be used for another appropriate weak base drugs.
Effect of diluent types and soluble diluents particle size on the dissolution...Valentyn Mohylyuk
Effect of different diluents types on the dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using microcrystalline cellulose (Avicel PH-101), calcium hydrogen phosphate dihydrate (Emcompress) and sorbitol (Neosorb P100T). The decreasing of mentioned diluents possibility to slow down of model substances dissolution kinetics (at pH 6.8) had follow sequence: Avicel PH-101 > Emcompress > Neosorb P100T.Effect of soluble diluents particle size on dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using sorbitol (Neosorb P100T, Neosorb P60 W and Neosorb P30/60) and lactose monohydrate (Sorbolac 400, Granulac 200 and Capsulac 60). The particle size increasing of lactose monohydrate from 11 to 251 μm and sorbitol from 110 to 513 μm decreased dissolution kinetics of model substances from Kollidon SR matrix tablets. Keywords : matrix tablets, Kollidon SR, caffeine, trimetazidine, diluent, particle size.
The chapter deals with the preformulation studies that have to be considered while designing a dosage form and developing a formulation that is suitable for a patient. Here, physical and chemical properties of a drug substance are studied along with biopharmaceutical classification of drugs. Also a detailed study on the application of preformulation studies in different dosage forms are also studied.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
Preformulation and physicochemical property of the drugSHIVANEE VYAS
“It is the study of the physical and chemical properties of the
drug prior to compounding process”.
Preformulation commences when a newly synthesized drug shows sufficient pharmacologic promise in animal models towarrant evaluation in man.
These studies should focus on physicochemical properties of new compound that affect drug performance & development of efficaciouss dosage form.
This properties may provide;
A rationale for formulation design
Support the need for molecular modification.
Effect of diluent types and soluble diluents particle size on the dissolution...Valentyn Mohylyuk
Effect of different diluents types on the dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using microcrystalline cellulose (Avicel PH-101), calcium hydrogen phosphate dihydrate (Emcompress) and sorbitol (Neosorb P100T). The decreasing of mentioned diluents possibility to slow down of model substances dissolution kinetics (at pH 6.8) had follow sequence: Avicel PH-101 > Emcompress > Neosorb P100T.Effect of soluble diluents particle size on dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using sorbitol (Neosorb P100T, Neosorb P60 W and Neosorb P30/60) and lactose monohydrate (Sorbolac 400, Granulac 200 and Capsulac 60). The particle size increasing of lactose monohydrate from 11 to 251 μm and sorbitol from 110 to 513 μm decreased dissolution kinetics of model substances from Kollidon SR matrix tablets. Keywords : matrix tablets, Kollidon SR, caffeine, trimetazidine, diluent, particle size.
The chapter deals with the preformulation studies that have to be considered while designing a dosage form and developing a formulation that is suitable for a patient. Here, physical and chemical properties of a drug substance are studied along with biopharmaceutical classification of drugs. Also a detailed study on the application of preformulation studies in different dosage forms are also studied.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
Preformulation and physicochemical property of the drugSHIVANEE VYAS
“It is the study of the physical and chemical properties of the
drug prior to compounding process”.
Preformulation commences when a newly synthesized drug shows sufficient pharmacologic promise in animal models towarrant evaluation in man.
These studies should focus on physicochemical properties of new compound that affect drug performance & development of efficaciouss dosage form.
This properties may provide;
A rationale for formulation design
Support the need for molecular modification.
Solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability. The water soluble carriers used in preparation of solid dispersion enhance the dissolution rate of the poorly water soluble drug. This work reflects the improvement of Dissolution Characteristics as well as Bioavailability of poorly aqueous soluble drug Hydrochlorothiazide. It belongs to BCS class 2 i.e. it has poor water solubility but good permeability.
it provide a brief note on the drug excipient interaction and various technique to find it which is a part of preformulation studies. it gives help to mpharm(pharmaceutics) students. i.
Solubility enhancement technique of BCS Class II drug by Solvent EvaporatiomKaustav Dey
I am very happy to share with you my B.Pharm Final semester Presentation. The topic of the presentation was “SOLUBILITY ENHANCEMENT TECHNIQUE OF BCS CLASS II DRUG BY SOLVENT EVAPORATION TECHNIQUE – FORMULATION & EVALUATION" which i have done under the esteemed guidance of Dr. Goutam Kumar Jena. It was a great experience to deliver this topic infront of the expert jury. I would also like thank all my teammates especially Agniv Masanta for his efforts. I hope everyone of you will like presentation and the research and efforts behind it.Thank you for giving your precious time. #research #science #thankyou #experience #share
In the present study an attempt will be made to design oral disintegrating tablets of Sumatriptan succinate (anti migraine) by using treated agar and Croscarmellose sodium as a superdisintigrants with a view to provide a convenient means of administration to those patients suffering from difficulties in swallowing such as pediatric and geriatric patients and uncooperative mentally ill patients.
Improved Wetting For Improved Solubility and Dissolution of Candesartan Cil...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Similar to Interaction of weak base drug trimetazidine and Carbopol as further retardation in the matrix tablet (20)
Welcome to the 1st International
Student Conference on
Industrial Pharmacy
President SC ISPE
Our conference is a pioneering event hosted by the
Poznan University of Medical Sciences and will be held
on the 7th and 8th of December, 2023. This conference
is a great opportunity to advance knowledge in the
field of pharmacy and provides a platform for students
to showcase their work.
The Event enables students to develop knowledge
especially in the field of pharmaceutical industry.
Moreover, it offers students a unique opportunity to
present their research through poster sessions and
presentations, fostering academic and professional
growth.
Our lectures boasts an impressive lineup of
distinguished speakers hailing from Poland, the United
Kingdom, and the Czech Republic, representing both
academia and industry. Their expertise will provide
invaluable insights into the dynamic world of industrial
pharmacy. Additionally, attendees can look forward to
a memorable Gala Night and engaging workshop
IVIVC for Extended-Release Hydrophilic Matrix Tablets in Consideration of Bio...Valentyn Mohylyuk
Purpose
When establishing IVIVC, a special problem arises by interpretation of averaged in vivo profiles insight of considerable individual variations in term of time and number of mechanical stress events in GI-tract. The objective of the study was to investigate and forecast the effect of mechanical stress on in vivo behavior in human of hydrophilic matrix tablets.
Methods
Dissolution profiles for the marketed products were obtained at different conditions (stirring speed, single- or repeatable mechanical stress applied) and convoluted into C-t profiles. Vice versa, published in vivo C-t profiles of the products were deconvoluted into absorption profiles and compared with dissolution profiles by similarity factor.
Results
Investigated hydrophilic matrix tablets varied in term of their resistance against hydrodynamic stress or single stress during the dissolution. Different scenarios, including repeatable mechanical stress, were investigated on mostly prone Seroquel® XR 50 mg. None of the particular scenarios fits to the published in vivo C-t profile of Seroquel® XR 50 mg representing, however, the average of individual profiles related to scenarios differing by number, frequency and time of contraction stress. When different scenarios were combined in different proportions, the profiles became closer to the original in vivo profile including a burst between 4 and 5 h, probably, due to stress-events in GI-tract.
Conclusion
For establishing IVIVC of oral dosage forms susceptible mechanical stress, a comparison of the deconvoluted individual in vivo profiles with in vitro profiles of different dissolution scenarios can be recommended.
Wurster Fluidised Bed Coating of Microparticles: Towards Scalable Production ...Valentyn Mohylyuk
Suspension of microparticles in an easy-to-swallow liquid is one approach to develop sustained-release formulations for children and patients with swallowing difficulties. However, to date production of sustained-release microparticles at the industrial scale has proven to be challenging. The aim of this investigation was to develop an innovative concept in coating sustained-release microparticles using industrial scalable Wurster fluidised bed to produce oral liquid suspensions. Microcrystalline cellulose cores (particle size <150 μm) were coated with Eudragit® NM 30 D and Eudragit® RS/RL 30 D aqueous dispersions using a fluidised bed coater. A novel approach of periodic addition of a small quantity (0.1% w/w) of dry powder glidant, magnesium stearate, to the coating chamber via an external port was applied throughout the coating process. This method significantly increased coating production yield from less than 50% to up to 99% compared to conventional coating
process without the dry powder glidant. Powder rheology tests showed that dry powder glidants increased the tapped density and decreased the cohesive index of coated microparticles. Reproducible microencapsulation of a highly water-soluble drug, metoprolol succinate, was achieved, yielding coated microparticles less than 200 μm in size with 20-h sustained drug release, suitable for use in liquid suspensions. The robust, scalable technology presented in this study offers an important solution to the long-standing challenges of formulating sustained-release dosage forms suitable for children and older people with swallowing difficulties.
In order to produce smaller droplets and compensate for the bigger droplets caused
by high viscosity fluids one can increase the pressure of the fluid. This will reduce the
droplet size according to the formula below
No more sampling! The Distek Opt-Diss 410 in-situ fiber optic UV system measures directly in the vessel, eliminating the need for conventional sampling, and with-it consumables like filters, tubing and syringes, saving time, labor, and money. Moving light rather than liquids also allows generating near real-time dissolution data and nearly limitless sample points as frequently as every five seconds.
PATVIS APA: visual inspection system for automated particle analysisValentyn Mohylyuk
- in-line or at-line process measurements
- simple installation in r & d or production of solid dosage forms
- portable, ergonomic and tool free
- ATEX and FDA CFR 21 part 11 compliant
Purpose
Fluid-bed coating of microparticles using aqueous polymer dispersions is a challenge due to particle agglomeration. Agglomeration is an undesirable phenomenon especially for modified release products resulting in inconsistent and unreliable coating thickness and drug release profile. Due to the small particle size and relatively high coating level, the determination of agglomerated particles is complicated and cannot be performed by common methods such as sieve analysis and observation under light microscope.
The objective of this study was to investigate appropriate methods to determine the internal structure of coated microparticles to support decision making in the formulation and coating process development.
Purpose
Most oral dosage forms such as tablets and capsules are not suitable for older people with swallowing difficulties. Capsules opening and tablet crushing are commonly used to overcome this problem. In addition to safety and legal concerns, this approach cannot be applied to sustained release products because of the loss of their functionality, consequently causing dose dumping and, undesirable side effects and even toxicity. The number of appropriate medicines for older patients with swallowing difficulties is limited because of the absence of appropriate oral dosage forms. One of the most appropriate forms of medicines for patients with swallowing difficulties are liquid formulations.
To overcome the described issues in older patients with dysphagia, the present study aimed at the development of film-coated sustained release microparticles for use in redispersible multi-dose oral suspensions to ensure facilitated swallowing and acceptable shelf life.
The present study was aimed at the development of a redispersible multi-dose suspension based on coated microparticles to ensure easy swallowing and sustained release of metoprolol succinate. To provide sustained release of metoprolol succinate, the microparticles were prepared by drug loading and Eudragit NM coating in a fluid-bed coater. Compositions of the liquid suspension vehicle were selected to reduce solubility of metoprolol succinate. The effect of vehicle composition and suspension storage time at RT on drug leaching into the suspension vehicle and on the drug release profile were investigated. The approach allowed a redispersible multi-dose suspension of metoprolol microparticles which, after one month storage, displayed negligible drug leaching into the suspension vehicle and a sustained release profile comparable to the profile before storage.
2018.09.07. Development of multi-dose oral sustained release suspensions for ...Valentyn Mohylyuk
The present study was aimed at the development of a re-dispersible multi-dose suspension based on coated microparticles to ensure easy swallowing and sustained release of metoprolol succinate. To provide sustained release of metoprolol succinate, the microparticles were prepared by drug loading and Eudragit® NM coating in a fluid-bed coater. Compositions of the liquid suspension vehicle were selected to reduce solubility of metoprolol succinate. The effect of vehicle composition and suspension storage time at RT on drug leaching into the suspension vehicle and on the drug release profile were investigated. The approach allowed a re-dispersible multi-dose suspension of metoprolol microparticles which, after one month’s storage, displayed negligible drug leaching into the suspension vehicle and a sustained release profile comparable to the profile before storage.
2017.10.18. Обзор мероприятия: Индустрия 4.0: Тенденции в области фармацевтич...Valentyn Mohylyuk
Обзор мероприятия: Международная конференция «Индустрия 4.0: Тенденции в области фармацевтического производства, технологий и упаковки» 18 октября 2017
Course:
"Medicines for older adults: Getting prepared for the scientific and regulatory evolution"
Place: 07 to 08 November 2017, Hotel Das Weitzer, Graz,
Austria
Chairs: Sven Stegemann, Graz University of Technology, Graz, Austria; Capsugel Carsten Timpe, F. Hoffmann-La Roche Ltd., Basle, Switzerland
2016.02.17. Extract from PhD Dissertation (Mohylyuk Valentyn)Valentyn Mohylyuk
ANNOTATION
Mohylyuk V.V. Scientific and practical substantiation of formulation and technology of sustained release matrix tablets. Case study: Trimetazidine dihydrochloride. – Manuscript.
A thesis for the Candidate of Pharmacy Degree in specialty 15.00.01. – Technology of drugs, organization of pharmaceutical business and forensic pharmacy. – Shupyk National Medical Academy of Postgraduate Education, Kyiv, 2016.
Dissertation is dedicated to the study of factors affecting the release kinetics of freely soluble active pharmaceutical ingredient trimetazidine dihydrochloride (TMZ•2HCl) in vitro from matrix tablets produced using direct compression method.
Effect of soluble matrix formers on TMZ•2HCl release profile from matrix tablets was conducted. It was experimentally established that matrix former release prolongation possibility increased with increasing of possibility to form viscous solutions in water: Klucel HXF > Methocel K15M > Polyox WSR-301 > Kollidon K-90 for different polymers and Methocel K100M > K15M > K100LV for same polymers with different molecular weight. Slowdown of release in the release medium with pH 6.8 was due to the interaction of TMZ•2HCl and Carbopol 71G with rubber-like layer formation.
It was experimentally established that effect of insoluble matrix formers on TMZ•2HCl release profile from matrix tablets was in sequence: Ethocel 10 > Precirol ATO 5 ≈ Kollidon SR > Eudragit RSPO. Swelling of Kollidon SR matrix was due to elastic recovery of spherical shape of polymer particles and polyvinyl acetate swelling upon hydration.
Diluents type effect on TMZ•2HCl dissolution profile was investigated. Soluble (sorbitol), insoluble (calcium hydrogen phosphate dihydrate), insoluble and swellable (cellulose microcrystalline) diluents were used. Faster TMZ•2HCl release from Ethocel 10, Kollidon SR and Methocel K4M matrix tablets with sorbitol than Emcompress and Avicel PH-101 was established. During determination of Emcompress and Avicel PH-101 effect on release kinetics from matrix tablets with different matrix formers were established that release was faster using: Avicel PH-101 in insoluble unswellable matrix of Ethocel 10; Emcompress in insoluble swellable matrix of Kollidon SR; Avicel PH-101 in soluble swellable matrix of Methocel K4М. It was established that TMZ•2HCl release kinetics from matrix tablets with Ethocel 10, Kollidon SR and Methocel K4M and Emcompress diluent was higher in pH 1 medium than in pH 6.8 which is consistent with pH-dependent Emcompress solubility.
Soluble diluents particle size effect on TMZ•2HCl dissolution profile was also investigated. Decreasing of TMZ•2HCl dissolution kinetics from Ethocel 10 matrix tablets with lactose and sorbitol particle size increasing was established. The dissolution kinetics from Kollidon
«Тенденции в области фармацевтического производства и технологий в контексте развития украинского фармрынка»
Панельная дискуссия
Конференция началась с панельной дискуссии с участием двух экспертов, работающих в украинских фармацевтических компаниях, – андрея гоя, руководителя департамента исследований и разработок ПАО
«Фармак», и валентина могилюка, менеджера по
стратегическому развитию ООО «Юнифарма».
2016. Dosage Form Optimization: Technology to Advance the Patient-Centric Dru...Valentyn Mohylyuk
A supplement to American Pharmaceutical Review
September / October 2016
Dosage Form Optimization: Technology to Advance the Patient-Centric Drug-Development Process
Catalent Development
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Interaction of weak base drug trimetazidine and Carbopol as further retardation in the matrix tablet
1. Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 72 No. 6 pp. 1259ñ1261, 2015 ISSN 0001-6837
Polish Pharmaceutical Society
In case of soluble matrices, a hydrogel formed
after contact of matrix with medium and drug release
occurs either via drug diffusion through a network of
capillaries formed between compacted matrix former
or/and erosion of the matrix. Dependent on the aque-
ous drug solubility, one of the mechanisms could
dominate or combination of both takes place (1).
Despite that Carbopol 71G is crosslinked polyacrylic
acid and in principle is insoluble, the drug release
occurs similarly to the water soluble matrices includ-
ing erosion (2). Being a weak acid, Carbopol 71G
can interact with weak bases at pH about pKa = 6.1.
Trimetazidine dihydrochloride as a week base (pKa1
4.45, pKa2 9.14 (4)) can interact with Carbopol 71G.
Therefore, the aim of this work was to investigate the
trimetazidine-Carbopol interactions and their effect
on drug release from matrix tablet.
EXPERIMENTAL
Materials
API: Trimetazidine dihydrochloride (TMZ ◊
2HCl, Sochinaz SA, Switzerland); matrix former:
crosslinked polyacrylic acid (Carbopol 71G,
Lubrizol Corp., USA); filler: lactose monohydrate
(Granulac 200, Meggle AG, Germany); glidant: col-
loidal silicon dioxide (Aerosil 200 Ph, Evonik AG,
Germany), lubricant: sodium stearyl fumarate (Pruv,
JRS Pharma, Germany).
Tablets preparation
Direct compression method was applied to
obtain 200 mg biconvex tablets with 8 mm diameter
according to the formulation presented in Table 1
using a mixer (Turbula T2F, Willy A. Bachofen AG,
Switzerland) and eccentric tablet press (Korsch
EKO, Korsch AG, Germany).
Dissolution test
The drug release from tablets was investigated
in a paddle apparatus (Vankel VK 300, Vankel
Industries, Edison., NJ, USA) at following condi-
tions: 900 mL of 0.1 M HCl or PBS pH 6.8, 100
rpm, 37O
C; (n = 3). Samples were withdrawn at pre-
determined time points, filtered through 0.35 µm fil-
ters and measured UV-spectrophotometrically at λ =
269 nm (pH 1: y = 0.0022x, R2
= 0.9999; pH 6.8: y
= 0.0022x + 0.0276, R2
= 0.9993).
Aqueous solubility determination
The shake-flask method was used for TMZ ◊
2HCl and Granulac 200 solubility determination.
INTERACTION OF WEAK BASE DRUG TRIMETAZIDINE AND CARBOPOL
AS FURTHER RETARDATION IN THE MATRIX TABLET
VALENTYN V. MOHYLYUK* and LENA L. DAVTIAN
Department of Pharmaceutical Technology and Biopharmaceutics, Shupyk National Medical Academy of
Postgraduate Education, Kyiv, Ukraine
Abstract: Hydrophilic polymers using as matrix former in matrix tablets is a common approach and well-
known excipient Carbopol is widely used for this reason too. In common case polymer doesnít interact with
drug but Carbopol is a weak polyacrylic acid and obviously can interact at physiological enteric conditions with
weak base drugs like trimetazidine dihydrochloride. During matrix tablet dissolution at enteric conditions, the
microenvironment pH inside tablet changes from surface to center. It was found that hydrated matrix has unusu-
al structured in microenvironment pH diapason of possible trimetazidine-Carbopol interactions. This matrix
structuration resulted in significant matrix behavior changing and increasing trimetazidine release retardation
in comparison with release data at gastric conditions. Thus, the example of trimetazidine-Carbopol interactions
demonstrate additional mechanism of drug retardation that could be used for another appropriate weak base
drugs.
Keywords: Carbopol, trimetazidine, matrix tablet, release retardation
1259
* Corresponding author: e-mail: Valentyn.Mohylyuk@gmail.com
2. 1260 VALENTYN V. MOHYLYUK and LENA L. DAVTIAN
The excess of tested substance was added to 50 mL
of medium (0.1 M HCl or PBS pH 6.8). The equi-
librium concentration was achieved in three days.
The substance solubility was calculated after drying
of known quantity of aliquot to constant weight at
105O
C.
RESULTS AND DISCUSSION
TMZ ◊ 2HCl release from matrix tablets at pH
1 was much faster than at pH 6.8 (Fig. 1) or slowed
down upon medium change from pH 1 to pH 6.8
after 2 h.
Since the solubility of Granulac 200 and TMZ
◊ 2HCl is relatively pH independent in the range 1-
6.8 (Tab. 2), the ionic interaction between positive-
ly charged TMZ and negatively charged Carbopol
71G could be a reason for slower drug release.
The swelling/erosion behavior of acidic disso-
lution medium (e.g., pH 1) of Carbopol 71G con-
taining tablets was not affected by the presence of
TMZ ◊ 2HCl (Fig. 2). In this medium, Carbopol
71G was not ionized and no interaction with TMZ ◊
2HCl occurred. The release of freely soluble drug
from swollen tablets was driven by diffusion and
was relatively fast (Fig. 1).
In the medium with pH 6.8, approx. 80 % of
carboxyl groups of Carbopol 71G and almost all ter-
tiary amine groups of TMZ were ionized (according
to pKa1) and can interact with each other forming
salt in a form of erodible gel layer (Fig. 3) on the
surface of the tablet. Tablets containing TMZ (F1)
did not swell in this medium in contrast to drug free
(F2) tablets (Fig. 2).
The increased swelling and viscosity of ionized
Carbopol 71G in the dissolution medium with pH
6.8 is well known phenomenon (3). However, due to
interaction with ionized TMZ, drug containing
tablets did not swell but rather eroded (Fig. 2). pH
measurement of different regions of tablet cross-sec-
tion after 5 h of dissolution test in phosphate buffer
pH 6.8 showed a pH gradient inside of tablets (Fig.
3 D). Cone-shaped rolled strips of indicator paper
which allows inserting the paper into a point was
used to pH determination. The pH decreased from
approx. 7 on the surface to 2-3 in the centre of the
tablet. A thin erodible surface layer which contacts
with PBS pH 6.8 organoleptically looks like mucus
(Fig. 3 A). The pH 5-7 in outer layer corresponds to
ionized state of Carbopol 71G and TMZ ◊ 2HCl,
where the interaction was possible. This outer layer
has rubber-like structure with elastic properties (Fig.
Table 1. Tablet composition (% per 200 mg tablet)
Formulation F1 F2
TMZ ◊ 2HCl 17.5 ó
Granulac 200 31.3 48.8
Carbopol 71G 50
Aerosil 200 Ph. and Pruv 0.2 and 1.0
Table 2. Aqueous solubility of TMZ ◊ 2HCl and Granulac 200 (n = 3, SD ≤ 5%)
Solubility (mg/mL) at pH
Compounds corresponding to
Stomach Small intestine
TMZ ◊ 2HCl 620 (pH 0.6) 340 (pH 6.7)
Granulac 200 210 (pH 0.9) 210 (pH 6.5)
Figure 1. Effect of medium pH on drug release
3. Interaction of weak base drug trimetazidine and carbopol as... 1261
3 B). The central part of tablet cross-section, which
corresponds to pH 2-5, has a form of plastic gel (Fig.
3 C) easy separable from outer layer. In contrast to
TMZ tablets (F1), the drug free tablet (F2) in PBS
pH 6.8 swelled without formation of internal struc-
ture and different way eroded (Fig. 3). After 19 h of
dissolution test in PBS pH 6.8 (Fig. 2), the solid
residue of drug free tablet (F2) was lower than solid
residue of TMZ contain tablet (F1) in spite of lower
solubility of Granulac 200 than TMZ ◊ 2HCl.
The different behavior of TMZ containing
tablet during dissolution test in 0.1 M HCl solution
in contrast to PBS pH 6.8, the behavior difference of
TMZ containing tablet in PBS pH 6.8 in contrast to
drug free tablet, the internal structure formation of
TMZ containing tablet in PBS pH 6.8 in contrast to
drug free tablet allow us to ascertain the presence of
TMZ-Carbopol 71G interaction. It seems that found
interaction of Carbopol 71G and TMZ in the outer
layer could be used for retardation of drug release.
CONCLUSION
Slowdown of release in the release medium
with pH 6.8 was due to the interaction of TMZ ◊
2HCl and Carbopol 71G with rubber-like layer for-
mation. This interaction could be used for further
retardation. Different release rate and mechanical
properties of tablet in different physiological pH
could provide problems for in vitro/in vivo correla-
tion because of unpredictable tablet presence in the
stomach. Therefore, one of the approaches to
achieve this retardation in pH independent manner
would be an enteric coating.
REFERENCES
1. Aulton M.E.: Pharmaceutics: the Science of
Dosage Form Design, 2nd edn., pp. 289-305,
Churchill Livingstone, Edinburgh 2002.
2. Lubrizol Advanced Materials Inc.,
Pharmaceutical Polymers for Oral Solid Dosage
Forms, Technical Data Sheet, 2011.
3. Lubrizol Advanced Materials Inc., Neutralizing
Carbopol and Pemulen Polymers in Aqueous
and Hydroalcoholic Systems, Technical Data
Sheet, 2009.
1. Reymond F. Steyaert G., Carrupt P.A., Morin
D., Tillement J.P. et al.: Pharm. Res. 16, 616
(1999).
Received: 15. 03. 2015
Figure 2. Matrix tablets behavior during dissolution test Figure 3. TMZ ◊ 2HCl containing matrix tablet after 5 h of disso-
lution test at pH 6.8: A) whole tablet, B) separated rubber-like
layer, C) separated gel core, D) cross-section
5. EDITOR
Aleksander P. Mazurek
National Medicines Institute, The Medical University of Warsaw
ASSISTANT EDITOR
Jacek Bojarski
Medical College, Jagiellonian University, KrakÛw
EXECUTIVE EDITORIAL BOARD
The Medical University of Warsaw
The Medical University of Warsaw
The Medical University of GdaÒsk
The Medical University of Warsaw
K. Marcinkowski University of Medical Sciences, PoznaÒ
The Medical University of Wroc≥aw
Polish Pharmaceutical Society, Warsaw
Czech Pharmaceutical Society
Charles Sturt University, Sydney
Pharmazeutisches Institut der Universit‰t, Bonn
DOV Pharmaceutical, Inc.
Semmelweis University of Medicine, Budapest
Miros≥awa Furmanowa
Boøenna Gutkowska
Roman Kaliszan
Jan Pachecka
Jan Pawlaczyk
Janusz Pluta
Witold Wieniawski
Pavel Komarek
Henry Ostrowski-Meissner
Erhard Rˆder
Phil Skolnick
Zolt·n Vincze
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6. Acta Poloniae Pharmaceutica ñ Drug Research
Volume 72, Number 6 November/December 2015
CONTENTS
REVIEW
1059. Syed Majid Bukhari, Iftikhar Ali, Asma Zaidi, Pharmacology and synthesis of daurichromenic acid as a
Naseem Iqbal, Tayyaba Noor, Rashad Mehmood, potent anti-HIV agent.
Muhammad Salman Chishti, Basit Niaz, Umer Rashid,
Muhammad Atif
1073. Mingwei Mou, Chungen Li, Minghua Huang, Antiosteoporotic effect of the rhizome of Drynaria fortunei
Ziyi Zhao, Huadong Ling, Xiang Zhang, (Kunze) (Polypodiaceae) with special emphasis on its modes
Fengxian Wang, Xincheng Yin, Yanxu Ma of action.
ANALYSIS
1081. Robert Piech, Beata Paczosa-Bator Application of glassy carbon electrode modified with
naftion/MWCNTS for sensitive voltammetric determination
of thymol.
1089. Kamil Kuú, Agnieszka Zakrzewska, Maria Walczak, Validation of LC/MS/MS method for assessment of the in vitro
Ma≥gorzata Szafarz, Anna Gonciarz, Agnieszka Kij, activity of the selected rat cytochrome P450 isoenzymes -
Joanna Suraj, Joanna Szymura-Oleksiak application to early drug metabolism screening.
1101. Urszula Hubicka, Pawe≥ Ømudzki, Barbara Øuromska- Determination and characterization of selected fluoroquinolones
Witek, Pawe≥ Zajdel, Jan Krzek oxidation products under potassium permanganate treatment.
1115. Wei Chen, Lin Li, Tuling Lu, Baochang Cai, Development of a quality control method for Schisandrae
Fangzhou Yin, Wu Yin Chinensis Fructus with micellar electrokinetic capillary
chromatography.
1125. Renata Paprocka, Boøena Modzelewska-Banachiewicz Determination of lipophilicity parameters of new derivatives of
N3
substituted amidrazones by reversed phase thin-layer
chromatography.
1133. Pawe≥ Olczyk, Katarzyna Komosinska-Vassev, Application of electron paramagnetic resonance spectroscopy for
Pawe≥ Ramos, £ukasz Mencner, Krystyna Olczyk, examination of free radical scavenging properties of insulin
Barbara Pilawa analogs.
1141. Ma≥gorzata Do≥owy, Alina Pyka The effect of β-cyclodextrin on the resolution of free and
conjugated forms of deoxycholic and chenodeoxycholic acids by
TLC-densitometry.
DRUG BIOCHEMISTRY
1151. Anna Pude≥ko, Ewa Obuchowicz Desipramine, fluoxetine and tranylcypromine have different
effects on apoptosis induced in rat cortical neurons by oxygen-
glucose deprivation.
1163. Agnieszka Bia≥ek, Andrzej Tokarz, Pawe≥ Zagrodzki Conjugated linoleic acids (CLA) decrease the breast cancer risk in
DMBA-treated rats.
1177. Pawe≥ Olczyk, Katarzyna Komosinska-Vassev, Interactions of Insuman Comb 25 insulin with free radicals -
Pawe≥ Ramos, Krystyna Olczyk, Barbara Pilawa kinetics examination by electron paramagnetic resonance
spectroscopy.
DRUG SYNTHESIS
1183. Saleh I. Alqasoumi, Mansour S. Alsaid, Maged S. Semisynthesis of novel sulfonamides, thioureas, and
Abdel-Kader, Mostafa M. Ghorab biphenylsulfones as a new class of anticancer agents
by using L-norephedrine as strategic starting material.
1193. Korany A. Ali, Mohamed A. Elsayed, Salwa Synthesis and antitumor screening of some new 2,6-bispyridines
M. Elhallouty, Khaled Mahmoud, Ahmad M. Farag functionalized with pyrazole-based heterocycles.
APPHAX 72 (6) 1057 ñ 1320 (2015)
7. NATURAL DRUGS
1201. Aminu Mohammed, Neil Anthony Koorbanally, Phytochemistry, anti-oxidative and anti-diabetic effects of various
Md. Shahidul Islam parts of Eugenia caryophyllata Thunb. in vitro.
1217. Agnieszka Kicel, Monika Anna Olszewska, Preliminary study on the composition of volatile fraction of fresh
Aleksandra Owczarek, Maria Wolbiú flowers and leaves of Robinia pseudoacacia L. growing in Poland.
1223. Youshan Li, Qi Zheng, Jianhui Qin Effect of TCM Yinhuangsan on rat's diabetic ulcer healing
morphology and recovery factors.
1233. Imran Shair Mohammad, Haji Muhammad Shoaib Khan, In vitro characterization and assessment of cosmetic potentials of
Atif Iqbal Arshad, Hira Ijaz, Parikshit Banerjee, W/O emulsion cream containing 2% Prosopis cineraria extract.
Asif Ullah Khan, Aftab-Ullah, Ajkia Zaman Juthi
1239. Aleksandra Owczarek, Jan Gudej, Monika Anna Antioxidant activity of Geum rivale L. and Geum urbanum L.
Olszewska
PHARMACEUTICAL TECHNOLOGY
1245. Ramzi Shawahna, Mashhour Ghanem, Ayat Ghanem, Establishing similarity between multisource betahistine
Abdul-Fattah Mansour, Nema Ahmad, Abdel Naser Zaid hydrochloride oral dosage forms using in vitro methods.
1253. Przemys≥aw Zalewski, Daria Szymanowska-Powa≥owska, The radiolytic studies of ceftriaxone in the solid state.
Piotr Garbacki, Magdalena Paczkowska, Alicja
TalaczyÒska, Judyta Cielecka-Piontek
1259. Valentyn V. Mohylyuk, Lena L. Davtian Interaction of weak base drug trimetazidine and carbopol as
further retardation in the matrix tablet.
1263. Przemys≥aw Zalewski, Robert SkibiÒski, Alicja Kinetics and mechanism of degradation of cefozopran
TalaczyÒska, Magdalena Paczkowska, Piotr Garbacki, hydrochloride in the solid state.
Judyta Cielecka-Piontek, Anna JeliÒska
PHARMACOLOGY
1269. Mohammad Ayaz, Fazal Subhan, Jawad Ahmed, Citalopram and venlafaxine differentially augments antimicrobial
Arif-ullah Khan, Farhat Ullah, Abdul Sadiq, properties of antibiotics.
Nawazish-i-Husain Syed, Ihsan Ullah, Sajid Hussain
1279. Ewelina Dziurkowska, Marek Weso≥owski, Changes of salivary cortisol level after venlafaxine treatment.
Maciej Dziurkowski
GENERAL
1289. M·rton Argay, Andrea MeskÛ, Rom·na ZelkÛ, Therapy reminder message for Hungarian patients with type 2
Bal·zs HankÛ diabetes.
1295. Daniela Minarikova, Adamos Panayotis Electronic prescription services system in Greece - pilot study.
1303. Mariola Drozd, Kazimierz Drozd, Monika Safety of OTC analgesic drugs in the opinion of Polish patients -
Szkultecka-DÍbek, Anna Kijewska, Nina Kiepurska preliminary study.
SHORT COMMUNICATION
1315. Abdulmohsen H. Al Rohaimi Neuropharmacological and toxicity study of newly prepared N-[5-
(3-chloro-4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2-substituted
acetamides.