Ethylcellulose in Organic Solution or Aqueous Dispersion Form in Designing Taste-Masked Microparticles by the Spray Drying Technique with a Model Bitter Drug: Rupatadine Fumarate

The taste of drugs is an important factor affecting pharmacotherapy effectiveness, and obtaining formulations with acceptable organoleptic properties is still an ongoing issue in pharmaceutical technology. One of the innovative methods of taste masking is preparation of microparticles by the spray drying technique, utilizing polymers with different physicochemical properties. Rupatadine fumarate (RUP) is one of the newest antihistamines, with an innovative and multidirectional mechanism of action, and an extremely bitter taste. The aim of this work was to investigate the feasibility of utilizing organic or aqueous forms of ethylcellulose (EC) for the preparation of microparticles with RUP by the spray drying technique. Spray dried samples at different drug:polymer ratios were prepared using organic solution (Ethocel®) or aqueous dispersions of EC (Surelease®, Aquacoat® ECD). Evaluation of the taste masking efficacy was performed in vivo in human taste panel, in vitro based on dissolution test, and by self-constructed electronic tongue. It was shown that microparticles obtained from aqueous dispersions of EC have superior pharmaceutical properties in terms of both morphology and taste masking efficacy in comparison to those obtained from organic solution.

Download Full-text

Characterization and taste masking evaluation of microparticles with cetirizine dihydrochloride and methacrylate-based copolymer obtained by spray drying

Acta Pharmaceutica ◽

10.1515/acph-2017-0002 ◽

2017 ◽

Vol 67 (1) ◽

pp. 113-124 ◽

Cited By ~ 8

Author(s):

Aleksandra Amelian ◽

Marta Szekalska ◽

Patrycja Ciosek ◽

Anna Basa ◽

Katarzyna Winnicka

Keyword(s):

Spray Drying ◽

In Vitro Release ◽

Electronic Tongue ◽

Butyl Methacrylate ◽

Masking Effect ◽

Taste Masking ◽

In Vivo Model ◽

Allergy Treatment

Abstract Taste of a pharmaceutical formulation is an important parameter for the effectiveness of pharmacotherapy. Cetirizine dihydrochloride (CET) is a second-generation antihistamine that is commonly administered in allergy treatment. CET is characterized by extremely bitter taste and it is a great challenge to successfully mask its taste; therefore the goal of this work was to formulate and characterize the microparticles obtained by the spray drying method with CET and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 copolymer (Eudragit E PO) as a barrier coating. Assessment of taste masking by the electronic tongue has revealed that designed formulations created an effective taste masking barrier. Taste masking effect was also confirmed by the in vivo model and the in vitro release profile of CET. Obtained data have shown that microparticles with a drug/polymer ratio (0.5:1) are promising CET carriers with efficient taste masking potential and might be further used in designing orodispersible dosage forms with CET.

Download Full-text

Utilization of Ethylcellulose Microparticles with Rupatadine Fumarate in Designing Orodispersible Minitablets with Taste Masking Effect

Materials ◽

10.3390/ma13122715 ◽

2020 ◽

Vol 13 (12) ◽

pp. 2715

Author(s):

Katarzyna Wasilewska ◽

Patrycja Ciosek-Skibińska ◽

Joanna Lenik ◽

Stanko Srčič ◽

Anna Basa ◽

...

Keyword(s):

Electronic Tongue ◽

Drug Dissolution ◽

Masking Effect ◽

Taste Masking ◽

Crucial Issue ◽

Geriatric Population ◽

Hydrophobic Polymer ◽

Pharmaceutical Properties

Minitablets in orodispersible form constitute a flexible drug delivery tool for paediatric and geriatric population as they eliminate the risk of chocking and do not require drinking water in the application. Due to their direct contact with taste buds, taste sensation is an important factor. Preparing microparticles with taste masking polymers utilizing spray drying is an efficient technique for reducing the bitterness of drugs. Ethylcellulose is a hydrophobic polymer widely used as a taste masking material. Rupatadine fumarate, one of the newest antihistamines, features an intensive bitter taste, hence in designing orodispersible formulations, achieving an acceptable taste is a crucial issue. The main objective of this work was to formulate orodispersible minitablets containing taste masked ethylcellulose-based microparticles with rupatadine fumarate and evaluation of their quality, especially in terms of taste masking efficacy. The accessed data indicated that all obtained minitablets were characterized by beneficial pharmaceutical properties. Three independent methods: in vivo with healthy volunteers, in vitro drug dissolution, and “electronic tongue” confirmed that all designed formulations provided satisfactory taste masking rate and that formulation F15 (prepared with Pearlitol® Flash and Surelease® microparticles with rupatadine fumarate) was characterized by the lowest bitterness score.

Download Full-text

Multi-Methodological Quantitative Taste Assessment of Anti-Tuberculosis Drugs to Support the Development of Palatable Paediatric Dosage Forms

Pharmaceutics ◽

10.3390/pharmaceutics12040369 ◽

2020 ◽

Vol 12 (4) ◽

pp. 369 ◽

Cited By ~ 2

Author(s):

Alison V. Keating ◽

Jessica Soto ◽

Claire Forbes ◽

Min Zhao ◽

Duncan Q. M. Craig ◽

...

Keyword(s):

Rank Order ◽

Electronic Tongue ◽

Taste Masking ◽

Assessment Data ◽

Taste Response ◽

Life Saving ◽

Taste Assessment ◽

Therapeutic Doses

The unpalatability of antituberculosis drugs is often cited as a major cause of non-adherence in children, yet limited quantitative taste assessment data are available. The aim of this research was to quantify the bitterness of isoniazid, rifampicin, pyrazinamide, and ethambutol dihydrochloride using two in vivo (a human taste panel and a rat brief-access taste aversion (BATA) model) and one in vitro (sensor) method. The response of the Insent TS-5000Z electronic tongue was compared to the in vivo drug concentration found to elicit and suppress half the maximum taste response (EC50 in human and IC50 in rats). Using dose-relevant concentrations, an overarching rank order of bitterness was derived (rifampicin > ethambutol > pyrazinamid~isoniazid). In vitro, only ethambutol exhibited a linear response for all sensors/concentrations. Based on the EC50/IC50 generated, a ‘taste index’ was proposed to allow for anticipation of the likelihood of taste issues in practice, taking in account the saturability in the saliva and therapeutic doses; ethambutol and isoniazid were found to be the worst tasting using this measure. The study presents the first quantitative taste analysis of these life-saving drugs and has allowed for a comparison of three methods of obtaining such data. Such information allows the operator to identify and prioritise the drugs requiring taste masking to produce palatable formulations.

Download Full-text

Structural and in vitro in vivo evaluation for taste masking

Expert Opinion on Drug Delivery ◽

10.1080/17425247.2018.1535590 ◽

2018 ◽

Vol 15 (11) ◽

pp. 1105-1116

Author(s):

Basheer Al-Kasmi ◽

Okba Al Rahal ◽

Hind El-Zein ◽

Abdul-Hakim Nattouf

Keyword(s):

Taste Masking ◽

In Vivo Evaluation

Download Full-text

Pharmaceutical properties of 'sucupira' (Pterodon spp.)

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502010000400002 ◽

2010 ◽

Vol 46 (4) ◽

pp. 607-616 ◽

Cited By ~ 15

Author(s):

Daiane Hansen ◽

Mitsue Haraguchi ◽

Antonio Alonso

Keyword(s):

Biological Effects ◽

Chemical Compounds ◽

Experimental Models ◽

Popular Medicine ◽

Isolation And Characterization ◽

Pharmaceutical Properties ◽

The Relationship

The plant of the genus Pterodon (Fabaceae, Leguminosae), commonly known as 'sucupira' or 'faveira', are disseminated throughout the central region of Brazil and has frequently been used in popular medicine for its anti-rheumatic, analgesic, and anti-inflammatory properties. In recent years, interest in these plants has increased considerably. The biological effects of different phytoextracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. The literature describes flavonoids, triterpene and steroids, while one paper presented studies with proteins isolated from the genus. This review provides an overview of phytochemical and pharmacological research in Pterodon, showing the main chemical compounds studied to date, and focusing on the relationship between these molecules and their biological activity. Furthermore, this study paves the way for more in-depth investigation, isolation and characterization of the molecules of this plant genus.

Download Full-text

FORMULATION, IN VITRO, AND IN VIVO EVALUATION OF TASTE-MASKED ORAL DISINTEGRATING TABLETS OF FEXOFENADINE HYDROCHLORIDE USING SEMISYNTHETIC AND NATURAL SUPERDISINTEGRANTS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i5.41558 ◽

2021 ◽

pp. 99-108

Author(s):

NAGADANI SWARNALATHA ◽

VIDYAVATHI MARAVAJHALA

Keyword(s):

Desirability Function ◽

Research Work ◽

In Vivo Studies ◽

Taste Masking ◽

Wet Granulation ◽

Maximum Plasma ◽

In Vivo Evaluation ◽

Eudragit Epo

Objective: The aim of the present research work was to prepare and evaluate taste-masked oral disintegrating tablets (ODT) of Fexofenadine hydrochloride. Methods: In the present work, Eudragit EPO, a taste masking agent and Karaya gum (GK) (natural), Sodium starch glycolate, and Croscarmellose sodium (CCS) (semi-synthetic) super disintegrants in three ratios (3, 6,9%) were used. Taste masked granules were prepared by different ratios of the drug: Eudragit EPO (1:1, 1:1.5, 1:2) by wet granulation method. The optimized taste-masked granules (1:2) were selected by sensory evaluation test to prepare 9 Fexofenadine ODT (FH1-FH9) formulations. These were evaluated for different parameters. Then desirability function (DF) was calculated for all formulations using disintegration time (DT), time taken for the tablet to release 90% of the drug (t 90%), and % drug dissolved in 10 min (Q10) as significant parameters. Results: The best formulation (FH6) showed the highest DF value due to less DT and 100% in vitro drug release within 15 min. Thus, FH6 formulation containing 9% CCS was selected as the best among the prepared formulations to which in vivo studies were performed on rabbits to find maximum plasma concentration (Cmax), time taken to reach maximum concentration (tmax), area under the curve (AUC), rate of elimination (Kel), absorption rate (Ka) and half-life(t1/2) and compared with Fexofenadine (Allegra) marketed tablets. Total bioavailability was increased for the test formulation compared to the reference formulation. Conclusion: Fexofenadine was successfully prepared as ODT with increased AUC and decreased tmax to which stability studies were conducted which were found to be stable.

Download Full-text

DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽

10.53879/id.57.08.12425 ◽

2020 ◽

Vol 57 (08) ◽

pp. 16-24

Author(s):

Mohammed Oday Ezzat ◽

Basma M. Abd Razik ◽

Kutayba F. Dawood

Keyword(s):

Angiotensin Converting Enzyme ◽

Active Site ◽

Docking Study ◽

World Health ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Pharmaceutical Properties ◽

Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

Download Full-text

TASTE MASKING OF OXYBUTYNIN CHLORIDE USING LIPID EXCIPIENTS AND FORMULATION AS ORODISPERSIBLE TABLETS FOR GERIATRIC POPULATION

INDIAN DRUGS ◽

10.53879/id.50.10.p0039 ◽

2013 ◽

Vol 50 (10) ◽

pp. 39-46

Author(s):

V Prakash ◽

◽

L. Keshri ◽

V. Sharma ◽

K. Pathak

Keyword(s):

In Vitro Release ◽

In Vitro Dissolution ◽

Taste Masking ◽

Dissolution Time ◽

Disintegration Time ◽

Geriatric Population ◽

Orodispersible Tablets ◽

Lipid Excipients

The aim of the present study was to mask the bitter taste of oxybutynin chloride by lipid excipients and to develop its fast disintegrating tablet. For this purpose, a blend of two lipids, glyceryl behenate and glyceryl palmitostearate was utilized for taste masking by solvent evaporation method. The evaporation of solvent was accomplished by freeze drying and taste masked granules were characterized for their micromeritic and rheological properties. The state of dispersion was analyzed by SEM and DSC. Orodispersible tablets were then formulated (F1- F6) using Polyplasdone XL as extragranular superdisintegrant and evaluated for hardness, disintegration time, in vitro dissolution time and in vivo disintegration time. Results indicated that the formulation F6 exhibited minimum in vivo disintegration time of 8 sec with effective taste masking. In vitro release analysis indicated %DE10 and %DE25 of 51.48 and 76.53 respectively. Conclusively, taste masked orodispersible formulation of oxybutynin chloride was developed that could be beneficial for geriatric population.

Download Full-text

Brazil Moves Toward the Replacement of Animal Experimentation

Alternatives to Laboratory Animals ◽

10.1177/0261192919856806 ◽

2019 ◽

Vol 47 (2) ◽

pp. 71-81 ◽

Cited By ~ 2

Author(s):

Renato Ivan de Ávila ◽

Marize Campos Valadares

Keyword(s):

Animal Experimentation ◽

Laboratory Animals ◽

National Council ◽

The European Union ◽

Innovative Methods ◽

Ethical And Legal Issues ◽

Research And Education ◽

Regulatory Acceptance

In Brazil, efforts towards the regulatory acceptance and implementation of innovative methods to replace experimental animal use in various fields began to gather force in 2008, with the approval of Law No. 11,794/2008 (the Arouca Law). This law represented a milestone, as it created the National Council for the Control of Animal Experimentation (CONCEA) to deal with the ethical and legal issues related to the use of laboratory animals. In 2014, CONCEA put together a framework for expanding the implementation of non-animal methodologies for use in research and education. It also promoted the regulatory acceptance in Brazil of 24 test guidelines, including 15 in vitro approaches. It should be emphasised that, in Brazilian legislation, replacement is generally based on the toxicological endpoint and not on the category of product, as tends to be the case in other countries (e.g. cosmetics in the European Union). The resolution-dependent deadlines for the obligatory replacement of in vivo methods with the CONCEA-approved tests are 2019 and 2021. Brazil has advanced considerably towards the replacement of animal experimentation, and in certain aspects, this has been in a highly progressive manner. However, there is still a lot of work to be done, especially considering the current political scenario with reduced investment in research, development and innovation. The chronology of significant events following the approval of the Arouca Law, which have contributed to the promotion of the Three Rs alternatives in Brazil, will be examined.

Download Full-text

An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation

Pharmaceutics ◽

10.3390/pharmaceutics12111032 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1032

Author(s):

Tânia Marante ◽

Cláudia Viegas ◽

Inês Duarte ◽

Ana S. Macedo ◽

Pedro Fonte

Keyword(s):

Spray Drying ◽

Polymeric Nanoparticles ◽

Therapeutic Proteins ◽

Pulmonary Delivery ◽

Non Invasive ◽

Rapid Absorption ◽

Technological Advances ◽

First Pass

The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.

Download Full-text