Bitter Taste Of Drug Research Articles

Optimization and In vitro Evaluation of Famotidine Loaded Effervescent Orally Disintegrating Tablets Using Central Composite Design

Background: Over the years, effervescent orally disintegrating tablets (ODTs) have proved their worth over conventional tablets in overcoming the swallowing problems associated with the geriatric and pediatric population. The addition of effervescent agents in ODT provides a rapid disintegration along with masking of the slight bitter taste of drugs and is worth exploring. Objective: The present research investigation deals with the preparation of effervescent ODTs by direct compression with rapid disintegration and adequate hardness using the central composite design response surface methodology. Methods: Central composite design was used to study the effect of concentration of crospovidone (X1) and concentration of citric acid and sodium bicarbonate (X2) as independent factors on the two responses: disintegration time (Y1) and drug release (Y2). The tablets were prepared by direct compression approach using directly compressible mannitol. Results: The optimization results obtained after application of ANOVA revealed that increase in the concentration of X1 and X2 resulted in the increase in disintegration time and % CDR. Following the statistical analysis of the results, the formulation batch (F-7) with a desirability index of 0.95 was chosen as optimized batch and exhibited 99±0.8 % release of the drug after 5 min, and rapid disintegrating time of 31±3 sec. All other tablet attributes were well within the official limits. Conclusion: The results obtained in the present investigation clearly revealed a successful development of famotidine effervescent ODTs with a better release profile in comparison to marketed formulation.

Formulation and Evaluation of Orodispersible Tablets Containing Taste Masked Mirabegron Resinate

The objective of present work was to develop taste masked orodispersible tablets of mirabegron. Mirabegron is beta 3 adrenoceptor agonist used to treat overactive bladder. Overactive bladder (OAB) is defined as a symptom syndrome showing feeling of urgency to urinate, typically accompanied by frequent daytime and nocturnal urination, in the absence of proven infection or other obvious pathology. Over active bladders are generally common in geriatrics. Moreover, this drug has a very strong bitter taste. Frequent dosing requires frequent water intake, which further aggregates the condition of over active bladder and bitter taste of drug affects patient compliance. Hence a need arises to mask the bitter taste for development of an ODT which does not require consuming water with every dosage. In this work, the bitter taste of mirabegron was masked by forming a complex with an ion exchange resin tulsion 344. The drug resin complexation process was optimized for resin activation, drug: resin ratio, soaking time and stirring time. In –vitro release studies revealed complete drug elution from the complex within 10 minutes in pH 1.2 buffer. The taste-masked complex was then formulated into palatable orodispersible tablets using a direct compression approach by use of superdisintegrants to achieve a rapid disintegration. The tablets were evaluated for weight variation, hardness, friability, drug content, wetting time, In- vivo disintegration time and in-vitro dissolution time.

Development, Formulation and Evaluation of Sustain Release Dispersible Tablet of Ornidazole

This Present research with dispersible tablet can compromise the efficacy and safety of the treatment to children’s and geriatric patients with masking the bitter taste of drug and developing its dispersible tablet. The purpose of this research work was to develop Dispersible tablet of Ornidazole by masking the bitter taste. Tablet containing drug and excipients were prepared by direct compression method. Excipients in combinations were incorporated to achieve the aim. Effect of different combinations was studied to optimize the ideal formulation. Drug excipients interaction studies were carried out by FTIR spectral analysis. The tablets were evaluated for their hardness, wetting time, disintegrating time and dissolution parameters. It was concluded that the tablets having the combination of Dried Mucilage (obtained from dried seeds of ocimum bacilicum) and Sodium starch glycolate met all the evaluation parameters and thus selected as the optimized formulation. Optimized formulation was undergone for stability testing as a parameter to predict the shelf life as per ICH guidelines and proved for its adequate shelf life.

Formulation Development and Characterization of Rapid Mouth Dissolving Film of Frovatriptan Succinate

NOTE: THE ARTICLE HAS BEEN RETRACTED BASED ON AUTHORS COMMUNICATION. Objectives: Aim of the present research work is to prepared rapid mouth dissolving film of frovatriptan Succinate. Methods: Rapid Dissolving Film is prepared by Solvent casting method, hydroxypropyl methylcellulose E3 and E15 are helpful in the film-forming polymer, plasticizer in propylene glycol disintegrant is croscarmellose sodium, the artificial sweetener in aspartame as, citric acid as saliva stimulant, xylitol as diluents and natural sweetener, wild cherry as a flavour and Brilliant blue dye for elegance was selected for Rapid Dissolving Film preparation. By prism, software result is obtained and then evaluated using analysis of variance (ANOVA). Results: The result suggested that the formulation containing 20% w/w aspartame, 10% w/w xylitol and 5% citric acid was found to effectively obscure the bitter taste of drug with best overall acceptability. The same composition of aspartame, citric acid and xylitol were used for further optimization using design of an experiment to continue obscuring the bitter taste of frovatriptan Succinate. Simple lattice mixture design which is helpful in drug formulation by using polymer plasticizer and disintegrant concentration for disintegration time-independent variable tensile strength and percentage elongation for the response. Conclusion: The effect of each variable, two and three-factor interactions were studied. The batches were numerically optimized to give a design space. Rapid mouth dissolving films are also found to behave better patient compliance in all the age groups. NOTE: THE ARTICLE HAS BEEN RETRACTED BASED ON AUTHORS' REQUEST.

Factorial Design Based Optimization of Hydroxyzine Hydrochloride Fast Dissolving Tablets

Hydroxyzine hydrochloride is a histamine H1 receptor antagonist used in the treatment for chronic urticaria, dermatitis, and histamine-mediated pruritus. Hydroxyzine hydrochloride has a bitter taste. The bitter taste of drug was masked by using a combination of flavor and complexing with β-cyclodextrines adopting solid dispersion technique. The taste masking ability of solid dispersions was evaluated by in vivo taste evaluation in healthy human volunteers. The Optimized taste masked solid dispersion of drug was developed as fast dissolving tablets by direct compression method using superdisintegrants like sodium starch glycolate, croscarmellose sodium and crospovidone in different concentration as per 23 factorial design model. Tablets were evaluated for their physico-chemical properties, in vitro release studies. The hardness (3.8-4.2 kg/cm2), friability (0.22 %-0.43 %), drug content (91.7 %-99.5 %) and disintegration time (3.24-4.22 min) of fast dissolving tablets were found uniform and within the specified limits. Analysis of variance was used to identify significant effect on disintegration time, Coefficient of determination R2=0.995. Obtained value of F was larger than critical F-value, and the result was found to be significant at that level of probability (p<0.05). Similar R2=0.9023 value was obtained in case of dissolution rate for F value and the result was found to be significant at that level of probability (p<0.05). From the statistical results, optimized formula F9 was developed which gave disintegration time of 3.58±0.87 min and in vitro drug release of 95.89 %. The formulations followed first order mechanism of release (r2=0.953-0.991). Hence taste masked Hydroxyzine hydrochloride fast dissolving tablets could be successfully developed using factorial design modele.

Overcome the challenges of drug administration in children by developing age-appropriate formulations

Interest in developing age-appropriate formulations of drugs to optimize pharmacological therapy in children continues to grow. With oral formulations being the most common route of administration, several factors relating to the formulation and bitter taste of drugs can impact the acceptability of medications in children. Approaches to improve medication acceptability include the use of alternative delivery systems, taste-masking strategies and the development of new technologies for formulation preparation.

Formulation, development and optimization of mouth dissolving tablets of Rizatriptan benzoate

Rizatriptan benzoate, a drug used to treat migraine needs quick action, for which mouth dissolving tablets (MDTs) of the drug may be suitable. However, the bitter taste of drug pose a major challenge to the development of MDTs of the drug. In the present study, MDTs were developed after masking the bitter taste of the drug through solid dispersion. The solid dispersions of Rizatriptan benzoate were prepared with PEG 6000 and mannitol in various ratios and the taste of the formulations was evaluated by willing volunteers and the most acceptable formulation was chosen for development of the MDTs. The MDTs were developed and optimized by using the sequential simplex optimization technique. Disintegration time, hardness and friability of the tablets were considered as the parameters for the optimization of formulations. The optimized formulation showed a disintegration time of 15 s, hardness of 5.2 kg/cm2 and friability of 0.5 %. The drug release of 99 % was achieved within 15 min in simulated saliva fluid. Therefore, the MDTs developed in this study could meet the dual need of effectively masking the bitter taste of the drug as well as deliver it quickly, for speedy onset of action and better therapeutic efficacy.

Design and development of co-processed excipients for fast dissolving tablets of Irbesartan by melt agglomeration technique

The co-processing is most widely explored method for development of directly compressible excipients. The present research was focused on development of co-processed excipients for fast dissolving tablets of Irbesartan by melt agglomeration technique. From the preliminary trials Lactose monohydrate and mannitol was selected as a diluent and Poly ethylene glycol 4000 as binder. To improve functionality of co-processed excipients 8 % crospovidone was incorporated. Diluent blend ratio and concentration of binder (%) were selected as independent variables in central composite design. The agglomerates were evaluated in terms of % fines, angle of repose, Carr’s index, Hausner ratio. The tablets were manufactured on a rotary press and their friability, tensile strength and disintegration time were evaluated. This optimized batch was characterized by means of the granular friability index, Heckel analysis, Kawakita, Kuno’s analysis, lubricant sensitivity ratio and a dilution potential study. Result of dilution potential showed that up to 40 % drug can be incorporated. In addition to these, bitter taste of drug was masked by forming drug—β-cyclodextrin inclusion complex and by adding aspartame as a Sweetener. Compared to conventional tablet it showed faster dissolution. Instrumental studies like Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction showed that the compatibility of various excipients with drug. The present study underlines the fact that melt granulation technique may be adopted for the development of directly compressible adjuvant for use in pharmaceuticals.

Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins

Context: The bitter taste of drug is masked by the exchange of ionized drugs with counter ions of ion exchange resin, forming “resinate”. Cyclodextrin reduces the unpleasant taste and enhances the drug solubility by encapsulating drug molecules into its central cavity.Objective: Oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin was developed, to mask the bitter taste and enhance drug dissolution.Methods: Meloxicam (MX) was selected as a model drug. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-β-cyclodextrin (HPβCD) or MX/HPβCD complexes, and a mixture of resinate and MX/HPβCD complexes) were made by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste and stability.Results and discussion: The tablet hardness was ∼3 kg/in2, and the friability was <1%. Tablets formulated with resinate and the mixture of resinate and MX/HPβCD complexes disintegrated rapidly within 60 s, which is the acceptable limit for ODTs. These results were corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HPβCD complexes provided complete MX dissolution and successfully masked the bitter taste. In addition, this tablet was stable at least 6 months.Conclusions: The combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste and enhance the dissolution of drugs that are weakly soluble in water.

Levocetirizine dihydrochloride and ambroxol hydrochloride oral soluble films: Design, optimization, and patient compliance study on healthy volunteers

Objective: The aim of this study was to develop taste masked oral soluble films (OSFs) for levocetirizine dihydrochloride (LCT) and ambroxol hydrochloride (AMB) using different combination of polymers such as polyvinyl pyrrolidone (PVP) K30, propylene glycol (PG), gelatin, sodium alginate (SA), pectin, gaur gum (GG), and hydroxypropyl methylcellulose (HPMC) K15M and super disintegrants like carboxymethyl cellulose (CMC) and sodium starch glycolate (SSG). Materials and Methods: The different basic formulations were developed using solvent casting method for with and without drugs loading and prepared films were evaluated different morphological and mechanical parameters facilitated the screening of a formulation with best characteristics. Results: The films made from HPMC K15M (42.2% w/w) and pectin (35.2% w/w) and considered as an optimized batch among the other formulations. The addition of (titanium dioxide) (TiO 2 ) films was shown opaque nature. The optimized films were subjected to further of drugs content, drugs release profile, stability, and organoleptic properties by human volunteers. The percentage release at end of 90 th s found 73.11 ± 5.2% in pH 6.0 and 81.07 ± 5.6% in water for LCT and 89.2 ± 4.5% in pH 6.0 and 86.22 ± 4.2% in water for AMB, respectively and there were insignificant changes showed at stability study. The organoleptic properties revealed that by complexing drugs with hydroxypropyl β-cyclodextrin (HPβ-CD) in 1:1.5 ratios masked the bitter taste of drugs. Conclusion: Developed OSFs can be considered as one of the promising formulation to administer bitter drugs such as LCT and AMB especially for pediatric, geriatric, and non-cooperative patients.

Practical Approaches for Taste Masking of Bitter Drug: A Review

Taste is most important organoleptic aspects about the acceptance of oral drugs. Bitter and unpalatable taste is a major problem of certain drugs in formulations. In market, there are numbers of pharmaceutical preparations available in which actives are bitter in taste. The improved palatability in these products has prompted the development of numerous formulations, which improved performance and acceptability. The bitterness of preparation also leads to patient incompliance. So masking of bitterness becomes essential and done by masking the bitter taste of drugs by either decreasing its oral solubility on ingestion or decreasing the amount of drug particles exposed to taste buds thereby reducing the perception of bitter taste. Methods commonly used for taste masking involves various physical and chemical method that prevent the interaction of taste bud with drugs and are based on coatings, solid dispersion system and ion exchange resin, entrapment method and masking of taste buds etc. Taste masking of bitter drugs become necessity in case of oral administration and selection of technology depends upon the bitterness of drugs and their compatibility with taste masking agents that does not affect the bioavailability of drug

Preparation of microcapsules masking the bitter taste of enoxacin by using one continuous process technique of agglomeration and microencapsulation.

In order to mask the bitter taste of drugs, a novel microencapsulation process combined with the wet spherical agglomeration (WSA) technique was developed by using a modified phase separation method. The spherical agglomerates of enoxacin (ENX) with various additives including disintegrants were successfully produced in the system of acetone-n-hexane-ammonia water or acetone-n-hexane-distilled water by the WSA, using flocculation phenomena of particles in liquid. Resultant agglomerates could be microencapsulated continuously with Eudragit RS utilizing the phase separation method in the same system as agglomeration under stirring. 'Explosible' microcapsules which were free from the bitter taste could be produced in formulating finer particle size of ENX and 50 per cent of Primojel in core agglomerates, using distilled water as a bridging liquid, and treating with 20 per cent polymer coating level. These microcapsules were bioequivalent to the commercial ENX 100 mg tablets in beagle dogs. One continuous process technique of agglomeration and microencapsulation was useful for the design of ENX powders which masked the bitter taste and controlled the drug release rate.