scholarly journals Benznidazole in vitro dissolution release from a pH-sensitive drug delivery system using Zif-8 as a carrier

2021 ◽  
Vol 32 (6) ◽  
Author(s):  
Leslie Raphael de Moura Ferraz ◽  
Alinne Élida Gonçalves Alves Tabosa ◽  
Débora Dolores Souza da Silva Nascimento ◽  
Aline Silva Ferreira ◽  
José Yago Rodrigues Silva ◽  
...  
Keyword(s):  
Public Health ◽  
Chagas Disease ◽  
Public Health Problem ◽  
Developed Countries ◽  
Dosage Forms ◽  
Ph Sensitive ◽  
In Vitro Dissolution ◽  
Prolonged Release ◽  
Migratory Movement

AbstractChagas disease is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). Endemic in underdeveloped and developed countries, due to the migratory movement, it is considered a serious public health problem. Endemic in underdeveloped countries and due to the migratory movement, in developed countries as well, it is considered a serious public health problem. One of the reasons for this is a weak therapeutic arsenal, represented only by the drug benznidazole (BNZ) which, although it promotes significant cure rates in the acute phase of the disease, presents serious problems of toxicity and bioavailability, mainly due to its low aqueous solubility. Several studies have presented several drug delivery systems (DDS) based on BNZ aiming at enhancing its solubility in aqueous medium and, with this, promoting an increase in the dissolution rate and, consequently, in its bioavailability. However, the present work is a pioneer in using a zeolitic imidazolate framework as a carrier agent for a DDS in order to promote a pH-sensitive modulation of the drug. Thus, this work aimed to develop a novel DDS based on BNZ and the ZIF-8 to use it in development of prolonged-release dosage forms to alternative treatment of Chagas disease. The BNZ@ZIF-8 system was obtained through an ex situ method selected due to its higher incorporation efficiency (38%). Different characterization techniques corroborated the obtainment and drug release data were analyzed by in vitro dissolution assay under sink and non-sink conditions and setting the kinetic results through both model dependent and independent methods. Under sink conditions, at pH 4.5, BNZ and BNZ@ZIF-8 showed similar release profile, but the DDS was effective in promoting a prolonged release. At pH 7.6, after 7 h, BNZ showed a lower release than BNZ@ZIF-8. On the other hand, in non-sink conditions at pH 4.5 the BNZ presented 80% of drug release in 3 h, while the DDS in 6 h. At pH 7.6, BNZ presented a release of 80% in 2 h, while the DDS reaches it in only at 12 h. Therefore, at pH 4.5 the DDS BNZ@ZIF-8 showed a faster release with a burst effect, while at pH 7.6 it showed a prolonged and controlled release. Finally, it is evident that a promising DDS pH-sensitive was obtained as a novel carrier that might be able to prolongs BNZ release in dosage forms intended for the alternative treatment of Chagas disease.

Development of new dinuclear Fe(III) coordination compounds with in vitro nanomolar antitrypanosomal activity

2021 ◽  
Author(s):  
Felipe Figuerôa Moreira ◽  
Juliana de Araujo Portes ◽  
Nathalia Florencia Barros Azeredo ◽  
Christiane Fernandes ◽  
Adolfo Horn ◽  
...  
Keyword(s):  
Public Health ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Health Problem ◽  
Coordination Compounds ◽  
Public Health Problem ◽  
Neglected Tropical Disease ◽  
Major Public Health Problem ◽  
Protozoan Pathogen

Chagas disease is a neglected tropical disease caused by the protozoan pathogen Trypanosoma cruzi. The disease is the major public health problem affecting about 6 to 7 million people worldwide,...

scholarly journals Development study of new topical formulations with erythromycin

2017 ◽  
Vol 10 (3) ◽  
pp. 109-115
Author(s):  
Lacramioara OCHIUZ ◽  
◽  
Andreea CRETEANU ◽  
Manuela HORTOLOMEI ◽  
Catalina Anisoara PEPTU ◽  
...  
Keyword(s):  
Permeability Coefficient ◽  
Macrolide Antibiotic ◽  
Dosage Forms ◽  
In Vitro Dissolution ◽  
Prolonged Release ◽  
Dissolution Test ◽  
Parent Molecule ◽  
Poorly Soluble ◽  
Scanning Electron

Erythromycin is a macrolide antibiotic prescribed for the topical treatment of acne. Pharmacologically, erythromycin has the disadvantage of being poorly soluble in water. This leads to formulation challenges in semisolid dosage forms. In recent years, many published studies have shown the ability of cyclodextrins to form complexes with drugs. These new complexes are characterized by much improved solubility and permeation compared to the „parent“ molecule. The aim of this study was to synthesize an inclusion complex of erythromycin and lactide-β-cyclodextrin for the formulation of semisolid bases and the development of innovative topical preparations with erythromycin. The erythromycin-lactide-βcyclodextrin complex was characterized by scanning electron microscopy and Fourier-transform infrared spectroscopy. Semisolid formulations were pharmacologically evaluated by in vitro dissolution test and kinetic analysis of drug release by fitting to representative mathematical models. The results obtained showed a prolonged release of erythromycin from erythromycin-lactide-β-cyclodextrin formulations and a higher permeability coefficient of these formulations compared to the erythromycin-based release.

Formulation and Evaluation of Bilayer Sustained Release Tablets of Salbutamol and Theophylline

2009 ◽  
Vol 2 (3) ◽  
pp. 638-646
Author(s):  
R. Nagaraju ◽  
Rajesh Kaza
Keyword(s):  
Ethyl Cellulose ◽  
Xanthan Gum ◽  
Dosage Forms ◽  
In Vitro Dissolution ◽  
Dissolution Studies ◽  
Sustained Release Tablets ◽  
Dissolution Apparatus ◽  
Single Dosage

Salbutamol and theophylline are available in conventional dosage forms, administered four times a day, leading to saw tooth kinetics and resulting in ineffective therapy. The combination of these two drugs in a single dosage form will enhance the patient compliance and prolong bronchodilation. Various polymers, such as hydroxy propyl methylcellulose K4M (HPMC- K4M), hydroxy propyl methylcellulose K100M (HPMC- K100M), xanthan gum, ethyl cellulose and hydroxy propyl methylcellulose phthalate (HPMC-P) were studied. HPMC-P and HPMC- K4M were found to be best in controlling the release. In-vitro dissolution studies were carried out for all the bi-layered tablets developed using USP dissolution apparatus type 2 (paddle). It was found that the tablet FB15-FW3 showed 50% release of salbutamol in first hour and the remaining was released for eight hours. However, theophylline was found to be released as per the USP specifications. The IR spectrum was taken for FB15-FW3 formulation and it revealed that there is no disturbance in the principal peaks of pure drugs salbutamol and theophylline. This further confirms the integrity of pure drugs and no incompatibility of them with excipients. Also, formulation of FB15-FW3 has shown required release pattern and complies with all the evaluated parameters and comparable to the marketed formulation.

scholarly journals The differences between the branded and generic medicines using solid dosage forms: In-vitro dissolution testing

2012 ◽  
Vol 2 ◽  
pp. 1-8 ◽  
Author(s):  
Mubarak Nasser Al Ameri ◽  
Nanda Nayuni ◽  
K.G. Anil Kumar ◽  
David Perrett ◽  
Arthur Tucker ◽  
...  
Keyword(s):  
Dosage Forms ◽  
In Vitro Dissolution ◽  
Dissolution Testing ◽  
Generic Medicines ◽  
Solid Dosage Forms ◽  
Solid Dosage

scholarly journals In Vitro and In Vivo Activities of E5700 and ER-119884, Two Novel Orally Active Squalene Synthase Inhibitors, against Trypanosoma cruzi

2004 ◽  
Vol 48 (7) ◽  
pp. 2379-2387 ◽  
Author(s):  
Julio A. Urbina ◽  
Juan Luis Concepcion ◽  
Aura Caldera ◽  
Gilberto Payares ◽  
Cristina Sanoja ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Public Health Problem ◽  
Squalene Synthase ◽  
Host Cells ◽  
In Vivo Studies ◽  
Inorganic Pyrophosphate ◽  
Orally Active

ABSTRACT Chagas' disease is a serious public health problem in Latin America, and no treatment is available for the prevalent chronic stage. Its causative agent, Trypanosoma cruzi, requires specific endogenous sterols for survival, and we have recently demonstrated that squalene synthase (SQS) is a promising target for antiparasitic chemotherapy. E5700 and ER-119884 are quinuclidine-based inhibitors of mammalian SQS that are currently in development as cholesterol- and triglyceride-lowering agents in humans. These compounds were found to be potent noncompetitive or mixed-type inhibitors of T. cruzi SQS with K i values in the low nanomolar to subnanomolar range in the absence or presence of 20 μM inorganic pyrophosphate. The antiproliferative 50% inhibitory concentrations of the compounds against extracellular epimastigotes and intracellular amastigotes were ca. 10 nM and 0.4 to 1.6 nM, respectively, with no effects on host cells. When treated with these compounds at the MIC, all of the parasite's sterols disappeared from the parasite cells. In vivo studies indicated that E5700 was able to provide full protection against death and completely arrested the development of parasitemia when given at a concentration of 50 mg/kg of body weight/day for 30 days, while ER-119884 provided only partial protection. This is the first report of an orally active SQS inhibitor that is capable of providing complete protection against fulminant, acute Chagas' disease.

scholarly journals SEROPREVALENCE OF CHAGASIC INFECTION IN YOUNG INDIVIDUALS IN A BLOOD CENTER IN THE STATE OF SAO PAULO, BRAZIL

2013 ◽  
Vol 55 (4) ◽  
pp. 245-250 ◽  
Author(s):  
Elaine Cristina Navarro ◽  
Renata Leme Goto ◽  
Isabella Silva Ricoboni ◽  
Jose Eduardo Corrente ◽  
Rita Maria Saccomano Henriques ◽  
...  
Keyword(s):  
Public Health ◽  
Chagas Disease ◽  
Blood Donors ◽  
Public Health Problem ◽  
Sao Paulo ◽  
São Paulo ◽  
Blood Center ◽  
Negative Results ◽  
Central Regions ◽  
The City

SUMMARY This study aimed at estimating the number of cases of non-negative serological reactions to Chagas disease in blood donors at the Blood Center of Botucatu, São Paulo, Brazil, from 2003 to 2010 and at relating them to their cities of origin. Five hundred and seventy-four non-negative results for Chagas disease were evaluated. Of these, 371 (64.8%) were reagent, and 203 (35.4%) were inconclusive. The prevalence of Chagas disease in blood donors was 0.05%. There were, on average, 72 cases/year, and a prevalence of males was observed (64.8%). Forty-three (7.49%) individuals were 18 to 30 years old; 92 (16.02%) were 31 to 40; 147 (25.61%) 41 to 50, and 292 (50.87%) were older than 50 years. It was observed that 29.3% of females with reagent serology were at their fertile age (18 and 45 years). The majority of donors were originally from cities in the southwestern and central regions of São Paulo, but individuals from other states contributed with 20%. The provenance of most donors was the city of Botucatu/SP, followed by the city of Taquarituba/SP. Therefore, the profile of donors at this blood center favors the occurrence of a larger number of non-negative serological reactions. Although there has been a significant reduction in the number of new cases/year for this disease, it is still a public-health problem, and results suggest the need for new epidemiological assessments in the studied region.

scholarly journals FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLET OF LORNOXICAM BY DIRECT COMPRESSION METHOD

2021 ◽  
Vol 10 (5) ◽  
pp. 131-136
Author(s):  
Asim pasha ◽  
C N Somashekhar
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Matrix Tablets ◽  
In Vitro Dissolution ◽  
Prolonged Release ◽  
Matrix Tablet ◽  
Direct Compression ◽  
Dissolution Profile ◽  
Drug Content

The aim of the present work was to develop sustained release Lornoxicam matrix tablets with polymers like HPMC K15M, Ethyl cellulose, and Crospovidone as carriers in varying quantities. Direct compression was used to make matrix tablets. Various assessment parameters, such as hardness, friability, thickness, percent drug content, weight variation, and so on, were applied to the prepared formulations. In vitro dissolution studies were carried out for 24 hrs. The tablets were subjected to in-vitro drug release in (pH 1.2) for first 2 hrs. Then followed by (pH 6.8) phosphate buffer for next 22 hrs. And the results showed that among the six formulations FL3 showed good dissolution profile to control the drug release respectively. The drug and polymer compatibility were tested using FT-IR spectroscopy, which revealed that the drug was compatible with all polymers. It is also required to design an appropriate prolonged release formulation for Lornoxicam in order to maintain the drug's release. Hence by using the compatible polymers sustained release tablets were formulated and subjected for various types of evaluation parameters like friability, hardness, drug content and dissolution behaviour. Finally, the findings reveal that the prepared sustained release matrix tablets of lornoxicam have improved efficacy and patient compliance.

scholarly journals Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Solange L. de Castro ◽  
Denise G. J. Batista ◽  
Marcos M. Batista ◽  
Wanderson Batista ◽  
Anissa Daliry ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Chronic Phase ◽  
Public Health Problem ◽  
Term Therapy ◽  
High Morbidity ◽  
Synthetic Compounds ◽  
Natural And Synthetic

Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi.

scholarly journals Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities

2021 ◽  
Vol 24 ◽  
pp. 548-562
Author(s):  
Matthias Shona Roost ◽  
Henrike Potthast ◽  
Chantal Walther ◽  
Alfredo García-Arieta ◽  
Ivana Abalos ◽  
...  
Keyword(s):  
Immediate Release ◽  
Dosage Forms ◽  
Oral Dosage ◽  
In Vitro Dissolution ◽  
Quantitative Composition ◽  
Modified Release ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

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