Design, Optimization And Evaluation Of Empagliflozin Orodispersible Tablets Using Different Superdisintegrants

Objective: The objective of this study was to formulate orodispersible tablets containing empagliflozin by direct compression method with sufficient hardness and rapid disintegration time and to study the effect of functionality differences of super-disintegrants on the tablet properties. Methods: A two factor three level factorial design (32) was used for the formulation optimization of orodispersible tablets of Empagliflozin and experimental trials were performed on all possible formulations, in which the amount of β-cyclodextrin, crospovidone and croscarmellose sodium were selected as independent variables (factor) varied at three different levels: low (-1), medium (0), and high (+1) levels. The drug release and disintegration time were used as dependent variables (response). All formulations were characterized for parameters such as diameter, hardness, weight, thickness, friability, disintegration time, drug release. Results: Formulation FD6 having 30 sec disintegration time, 98.84% drug release after 30 min, 2.8 kg/cm2 hardness and 0.292% friability was found best among all formulations and selected as an optimized formulation with rapid onset of action and enhanced bioavailability (more than 98% drug release within 30 min.) as compared to the oral empagliflozin tablet. Conclusion: Empagliflozin orodispersible tablets with different superdisintegrants were successfully prepared and formulation containing highest percentage of crospovidone was found best among all other formulations in terms of bioavailability and rapid onset of action.

Formulation and evaluation of orally disintegrating clopidogrel tablets

ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs) that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC). DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.

RESUMO Recentes avanC'os em sistemas de liberaC'C#o de fC!rmacos novos visam C obtenC'C#o de melhor adesC#o do paciente. Um destes avanC'os C) a formulaC'C#o de comprimidos de desintegraC'C#o oral (ODTs), que se dissolvem instantaneamente, liberando o fC!rmaco, em alguns segundos, sem a necessidade de C!gua. O principal objetivo deste trabalho foi preparar e desenvolver ODTs de clopidogrel. Os ODTs foram preparados pelo mC)todo de compressC#o direta. Estudou-se o efeito de vC!rias concentraC'C5es de diferentes agentes de desintegraC'C#o, tais como super-crospovidona, croscarmelose de sC3dio, glicolato de amido de sC3dio no tempo de desintegraC'C#o e velocidade de dissoluC'C#o. Os comprimidos preparados foram avaliados quanto C dureza, C friabilidade, ao tempo de desintegraC'C#o e C liberaC'C#o do fC!rmaco in vitro. AlC)m disso, estudou-se a interaC'C#o de clopidogrel com os excipientes de formulaC'C#o, utilizando calorimetria de varredura diferencial (DSC). Estudos de DSC revelaram nC#o haver interaC'C#o entre o fC!rmaco e os excipientes utilizados. Todos os comprimidos possuC-am dureza na faixa de 4,0-5,2 kp e a friabilidade inferior a 1%. A variaC'C#o de peso e o teor de fC!rmaco de todas as formulaC'C5es mostraram-se dentro do limite oficial, de acordo com a BP. O estudo de liberaC'C#o do fC!rmaco in vitro de comprimidos ODTs mostrou que mais de 90% do fC!rmaco foram liberados em10 minutos. O teste de palatabilidade em voluntC!rios humanos mostrou sabor e sensaC'C#o na boca aceitC!veis. Assim, os resultados obtidos demonstraram, conclusivamente, a rC!pida e bem-sucedida desintegraC'C#o dos comprimidos formulados e a palatabilidade aceitC!vel.

Contrasting the crospovidones functionality as excipients for direct compression

Specific values of technological properties of excipients allow the establishment of numerical parameters to define and compare their functionality. This study investigates the functionality of Polyplasdones XL and XL10. Parameters studied included tablet disintegration profiles, compactibility profiles and powder flow. The results allowed the establishment of quantitative surrogate functionalities of technological performance, such as absolute number, and as a value relative to the known microcrystalline cellulose type 102. Moreover, the establishment of an explicit functionality to improve the technological performance of two diluents and a model drug was investigated, as was setting up of these functionalities, as quantitative values, to determine the input variables of each material and its probable functionality in a drug product. Disintegration times of pure Polyplasdone XL and its admixtures were around half that of Polyplasdone XL10. The improvement in tablet compactibility was 25-50% greater for Polyplasdone XL10 than Polyplasdone XL. Crospovidones proportions of up to 10% have little effect on the flow properties of other powders, although pure Polyplasdone XL10 and its admixtures display compressibility indexes about 20% greater than Polyplasdone XL. The observed results are in line with a smaller particle size of Polyplasdone XL10 compared to Polyplasdone XL.

Os valores específicos de propriedades tecnológicas de excipientes permitem o estabelecimento de parâmetros numéricos para definir e comparar a sua funcionalidade. Este estudo investiga a funcionalidade dos excipientes. Os parâmetros estudados foram perfis de desintegração dos comprimidos, perfis de compactação e fluxo de pó. Os resultados permitiram expressar o desempenho tecnológico através de valores absolutos e valores relativos à conhecida celulose microcristalina tipo 102. Do mesmo modo, permitiram estabelecer uma funcionalidade explícita para melhorar o desempenho tecnológico de dois diluentes e um fármaco modelo. A criação destas funcionalidades, como valores quantitativos, permite conhecer as variáveis de entrada de cada material e sua provável funcionalidade em um medicamento. Os tempos de desintegração do Poliplasdone XL e das suas misturas são cerca da metade do observado para as misturas com o Poliplasdone XL10. Melhoria da compressão de comprimidos que contêm Polyplasdone XL10 é 25-50% maior do que o Polyplasdone XL. Crospovidonas em proporções de até 10% têm pouco efeito sobre as propriedades de fluxo dos outros pós embora o Poliplasdone XL10 e suas misturas exibam índices de compressibilidade cerca de 20% maior do que o Poliplasdone XL. Os resultados observados estão em sintonia com o menor tamanho de partícula do Poliplasdone XL10, em comparação com o Poliplasdone XL.

Formulation, Evaluation and Pharmacokinetics of Flurbiprofen Fast Dissolving Tablets.

Aim: The intent of present study is to formulate fast dissolving tablets of flurbiprofen using different superdisintegrants to improve the dissolution and bioavailability. Place and Duration of Study: Jyothishmathi Institute of Pharmaceutical Sciences, Karimnagar, Andhra Pradesh, India, between January 2011 and December 2012. Methodology: Flurbiprofen fast dissolving tablets were prepared using different superdisintegrants and characterized for different physical parameters, DSC, FTIR studies, in vitro dissolution studies and in vivo pharmacokinetics to prove the enhancement of bioavailability. Results: From the in vitro dissolution studies, the percent drug release in 15 min (Q15) was found to be 91.46±1.42% in case of optimized formulation where as the conventional tablets prepared by similar manner showed 22.92±0.47% in 15 min. The initial dissolution rate and dissolution efficiency for optimized formulation was 6.10%/min and 53.44 but it was 1.53%/min and 10.96 in conventional tablets. They increased by 4.0 folds when compared to conventional tablets. From the pharmacokinetic evaluation, the optimized fast dissolving tablets produced peak plasma concentration (Cmax) as 11433.32 ng/ml at 2 h Tmax, but they were found to be 8792.64 ng/ml at 3 h Tmax, in case of conventional tablets. The area under the curve for the optimized fast dissolving and conventional tablets were found to be 42691.23 and 30727.14 ng-h/ml. Conclusion: In summary, formulation of fast dissolving tablets using superdisintegrants was a good approach to enhance the dissolution and absorption rates of flurbiprofen.

Development of Fast Disintegration Tablets As Oral Drug Delivery System-A Review.

Fast disintegrating tablets (FDTs) have received increasing demand from the last few years and the field has become a rapidly growing field in the pharmaceutical industry. Fast disintegrating tablets (FDTs) are those solid doses form which when put on the tongue gets rapidly dissolved, releasing the drug within a few second without need of water. The development of FDTs have been formulated for paediatric, geriatric and bedridden patients and for active patients who are busy and travelling and may not have access to water. Such formulation provide an opportunity for product line extension in the many elderly persons will have difficulties in taking conventional oral doses forms (viz, solution suspensions tablet and capsules) because of hand tremors and dysphagia. This article focused on ideal requirements, need for development of FDTs, challenges in formulations, suitability of drug candidates superdisintegrants employed, various technologies developed for FDTs. Evaluation methods, and various marketed products.

Formulation and evaluation of fast dissolving tablet of albendazole.

Albendazole is broad spectrum anthelmintic use against many helminths. It is used for treatment of Threadworm, Hookworm, and Tapeworm. It has low bioavailability due to its first pass metabolism. In the present work, fast dissolving tablet of Albendazole was design with a view to and provide a quick onset of action. The main objective of the study was to formulate fast dissolving tablets of Albendazole to achieve a better dissolution rate and further improving the bioavailability of the drug. Fast dissolving tablets prepared by direct compression and using super disintegrants in different concentration and evaluated for the pre-compression parameters. The prepared tablets were evaluated for post compressional evaluation. Among all, the formulation F3 containing 5%w/w superdisintegrant Crospovidone and 20%w/w Microcrystalline Cellulose was considered to be best formulation, which release up to 99.097% in 40 min.

Formulation and evaluation of fast dissolving tablets of amlodipine besylate by using Fenugreek seed mucilage and Ocimum basilicum gum.

Fast dissolving/disintegrating tablets have received ever-increasing demand during the last decade, and the field has became a rapidly growing area in the pharmaceutical area. Particularly the fast dissolving drug delivery systems formulated with natural polymers have more demand because natural materials like gums and mucilages have been extensively used in the field of drug delivery for their easy availability, ease administration, non toxicity, non irritant nature etc. The main aim of the present study was to formulate the fast dissolving tablets of amlodipine besylate tablets using Fenugreek seed mucilage and Ocimum basilicum gum as a natural superdisintegrating agents to achieve quick onset of action, is to increase the water uptake with in shortest wetting time and there by decrease the disintegration time of the tablets by simple and cost effective direct compression technique. Pre-compression parameters like angle of repose and post-compression parameters like wetting time, water absorption ratio, in-vitro disintegration and in-vitro dispersion time were studied. The hardness, friability and drug content of all the formula-tions were found to be within the limits. The best formulations FFGK5 & FOB5 have shown good disintegration time, hardness and friability. The best formulations were also found to be stable. Optimized formulation was subjected to stability studies as per ICH guidelines and it insignificant change in hardness, disintegration time and in vitro drug release.

Solubility enhancement, physicochemical characterization and formulation of fast-dissolving tablet of nifedipine-betacyclodextrin complexes

The main objective of the study was to enhance the dissolution of nifedipine, a poorly water soluble drug by betacyclodextrin complexation and to study the effect of the preparation method on the in vitro dissolution profile. The stoichiometric ratio determined by phase solubility analysis for inclusion complexation of nifedipine with β-cyclodextrin was 1:1. Binary complex was prepared by different methods and was further characterized using XRD, DSC and FT-IR. A saturation solubility study was carried out to evaluate the increase in solubility of nifedipine. The optimized complex was formulated into fast-dissolving tablets by using the superdisintegrants Doshion P544, pregelatinized starch, crospovidone, sodium starch glycolate and croscarmellose sodium by direct compression. Tablets were evaluated for friability, hardness, weight variation, disintegration and in vitro dissolution. Tablets showed an enhanced dissolution rate compared to pure nifedipine.

Este estudo teve por objetivo principal incrementar a dissolução do nifedipino, fármaco pouco solúvel em água, por meio de sua complexação com β-ciclodextrina e estudar o efeito do método de preparação sobre o perfil de dissolução in vitro. A razão estequiométrica, determinada por ensaio de solubilidade de fase, para a complexação de nifedipino por inclusão em β-ciclodextrina foi 1:1. O complexo binário foi preparado por diferentes métodos, sendo caracterizado utilizando-se difratometria de raios X (XRD), calorimetria diferencial de varredura (DSC) e espectroscopia no infravermelho com transformada de Fourier (FT-IR). Realizou-se estudo de solubilidade de saturação para avaliar o incremento da solubilidade do nifedipino. O complexo otimizado foi formulado em comprimidos de dissolução rápida preparados por compressão direta, nos quais se utilizaram os superdesintegrantes Doshion P544, amido pré-gelatinizado, crospovidona, amidoglicolato de sódio e croscarmelose sódica. Os comprimidos, que foram avaliados quanto à friabilidade, dureza, variação de peso, desintegração e dissolução in vitro, apresentaram taxa de dissolução superior à do nifedipino pura.

Effect of superdisintegrants on formulation of taste masked fast disintegrating Ciprofloxacin tablets.

The present investigation deals with the formulation of taste masked fast disintegrating tablets of Ciprofloxacin that disintegrate in the oral cavity upon contact with saliva and thereby improve therapeutic efficacy. Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class. It is a second-generation fluoroquinolone antibacterial that kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and protein. It may also be used to prevent or slow anthrax after exposure. The influence of superdisintegrants, crospovidone and sodium starch glycolate on disintegration time, wetting time and water absorp-tion ratio were studied. Tablets were evaluation for weight and thickness variation, disintegration time, drug content, in vitro dissolution, wetting time and water absorption ratio. The in vitro disintegration time of the best fast disinte-gration tablets was found to be within 36 seconds. Tablets containing crospovidone (40%) exhibits quick disintegration time than tablets containing sodium starch glycolate. The fast disintegrating tablets of ciprofloxacin with shorter disintegration time, acceptable taste and sufficient hardness could be prepared using crospovidone and other excipients at optimum concentration.

Formulation Development and Evaluation of Acyclovir Orally Disintegrating Tablets.

Orally disintegrating systems have an edge amongst the oral drug delivery systems due to the highest component of compliance they enjoy in patients especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to withstand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. Therefore, research in developing orally disintegrating systems has been aimed at investigating different excipients as well as techniques to meet these challenges. Acyclovir is an antiviral drug used for the treatment of herpes simplex virus (HSV), mainly HSV-1 and HSV-2 and varicella zoster virus. It is a BCS class III drug. Hence an orally disintegrating tablet formulation of acyclovir was prepared by direct compression and wet granulation techniques after incorporating superdisintegrants croscarmellose sodium and sodium starch glycolate. Seven formulations were prepared. Tablet containing sodium starch glycolate showed excellent in vitro dispersion time and drug release as compared to other formulation. After study of seven formulations DT3 showed short dispersion time with maximum drug release in 10 min. It is concluded that fast disintegrating acyclovir tablets could be prepared by direct compression using superdisintegrants.

Formulation and evaluation of fast dissolving tablet of albendazole.

Albendazole is broad spectrum anthelmintic use against many helminths. It is used for treatment of Threadworm, Hookworm, and Tapeworm. It has low bioavailability due to its first pass metabolism. In the present work, fast dissolving tablet of Albendazole was design with a view to and provide a quick onset of action. The main objective of the study was to formulate fast dissolving tablets of Albendazole to achieve a better dissolution rate and further improving the bioavailability of the drug. Fast dissolving tablets prepared by direct compression and using super disintegrants in different concentration and evaluated for the pre-compression parameters. The prepared tablets were evaluated for post compressional evaluation. Among all, the formulation F3 containing 5%w/w superdisintegrant Crospovidone and 20%w/w Microcrystalline Cellulose was considered to be best formulation, which release up to 99.097% in 40 min.

Formulation and evaluation of fast dissolving tablets of amlodipine besylate by using Fenugreek seed mucilage and Ocimum basilicum gum.

Fast dissolving/disintegrating tablets have received ever-increasing demand during the last decade, and the field has became a rapidly growing area in the pharmaceutical area. Particularly the fast dissolving drug delivery systems formulated with natural polymers have more demand because natural materials like gums and mucilages have been extensively used in the field of drug delivery for their easy availability, ease administration, non toxicity, non irritant nature etc. The main aim of the present study was to formulate the fast dissolving tablets of amlodipine besylate tablets using Fenugreek seed mucilage and Ocimum basilicum gum as a natural superdisintegrating agents to achieve quick onset of action, is to increase the water uptake with in shortest wetting time and there by decrease the disintegration time of the tablets by simple and cost effective direct compression technique. Pre-compression parameters like angle of repose and post-compression parameters like wetting time, water absorption ratio, in-vitro disintegration and in-vitro dispersion time were studied. The hardness, friability and drug content of all the formula-tions were found to be within the limits. The best formulations FFGK5 & FOB5 have shown good disintegration time, hardness and friability. The best formulations were also found to be stable. Optimized formulation was subjected to stability studies as per ICH guidelines and it insignificant change in hardness, disintegration time and in vitro drug release.

Effect of superdisintegrants on formulation of taste masked fast disintegrating Ciprofloxacin tablets.

The present investigation deals with the formulation of taste masked fast disintegrating tablets of Ciprofloxacin that disintegrate in the oral cavity upon contact with saliva and thereby improve therapeutic efficacy. Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class. It is a second-generation fluoroquinolone antibacterial that kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and protein. It may also be used to prevent or slow anthrax after exposure. The influence of superdisintegrants, crospovidone and sodium starch glycolate on disintegration time, wetting time and water absorp-tion ratio were studied. Tablets were evaluation for weight and thickness variation, disintegration time, drug content, in vitro dissolution, wetting time and water absorption ratio. The in vitro disintegration time of the best fast disinte-gration tablets was found to be within 36 seconds. Tablets containing crospovidone (40%) exhibits quick disintegration time than tablets containing sodium starch glycolate. The fast disintegrating tablets of ciprofloxacin with shorter disintegration time, acceptable taste and sufficient hardness could be prepared using crospovidone and other excipients at optimum concentration.

Formulation and evaluation of orally disintegrating tablet containing tramadol hydrochloride by mass extrusion technique.

Orally disintegrating tablets are gaining popularity over conventional tablets due to their convience in administration and suitability for patients. The purpose of this research was to mask the intensely bitter taste of tramadol hydrochloride and to prepare orally disintegrating tablets for achievement of quick onset of action of the drug. Trammadol hydrochloride is an analgesic which has been proved to be efficient in managing relief from pain and including pain after surgery. In the present study an attempt has been made to prepare bitterless orally disintegrating tablet of Tramadol Hydrochloride using Eudragit E 100 as a taste masking agent. Mass extrusion was the technique used for preparing taste masked granules and tablet was prepared with using superdisintegrants like crospovidone, croscarmellose sodium and sodium starch glycolate, were prepared blend and evaluated for the pre-compression parameters such as bulk density, compressibility, angle of repose etc. The prepared batches of tablets were evaluated for hardness, weight variation, friability, drug content, disintegration time and in-vitro dissolution profile and found satisfactory. Among the formulations containing Crospovidone was least and tablets showed fastest disintegration. The drug release from orally disintegrating tablets increased with increasing concentration of superdisintegrants and was found to be highest with formulations containing Crospovidone. Thus results conclusively demonstrated successful masking of taste and fastest disintegration of the formulated tablets in oral cavity.

Levocetirizine orodispersible tablet by direct compression method.

Orodispersible tablets are those that dissolve or disintegrate quickly in the oral cavity, resulting in solution or suspension. Allergic rhinitis is a high-prevalence chronic respiratory disease with a negative impact on the subject’s quality of life, work activities, productivity or school performance as well as on healthcare costs. Because of its benign nature, the importance of this condition is often underestimated. In the present study orodispersible tablet of antihistaminic agent was prepared by direct compression method using crosspovidone, Crosscarmellose and Indion 414, as superdisintegrants. FT-IR study shows that there is no significant interactions occur between drug and excipient. The tablets prepared were evaluated for various parameters like various density parameters, thickness, hardness, friability, disintegration time, wetting time and In-vitro dissolution time. All the parameters were found to be within limits. The developed formulation of levocetirizine batch F8 (10% Indion 414) showed good palatability and dispersed within 30 seconds as compare to crosscarmellose sodium and crosspovidone. When the results were compared with that of convectional tablets was found to be better with respect to simple manufacturing and allergic rhinitis.

“Mouth dissolving tablets” an innovative technology.

Mouth dissolving tablets are disintegrating and dissolve rapidly in the saliva without the need for water. Some tablets are designed to dissolve in saliva remarkably fast, within a few seconds, and are true fast-dissolving tablets. Others contain agents to enhance the rate of tablet disintegration in the oral cavity, and are more appropriately termed fast-disintegrating tablets, as they may take up to a minute to completely disintegrate. Oral delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. Fast- or mouth dissolving tablets have been formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and traveling and may not have access to water.

Superdisintegrant Selection for Tramadol Dispersible Tablets

The selection of a suitable superdisintegrant for a rapidly disintegrating dosage form is of the utmost importance, since disintegration time (DT) is a critical parameter. An experimental design was implemented, to find out the effects of superdisintegrants (sodium starch glycolate, crospovidone, croscarmellose sodium and methacrylic copolymer with divinyl benzene), at 2, 4, 6% w/w, on tablet hardness, with respect to DT. Methacrylic copolymer with divinyl benzene (at 4 wt%) was selected as the best superdisintegrant, adequate for the formulation of dispersible Tramadol tablets. With increasing hardness, there was a considerable increase in DT at all concentrations of superdisintegrants. A combination of crospovidone and methacrylic copolymer with divinyl benzene showed a remarkable drop in DT to 0.33 min. The stability of the batch with lowest DT was also tested under various conditions and the results suggested that there was no degradation over the test period.

Novel approach in formulation and evaluation of mouth dissolving tablets of ondansetron hydrochloride.

Mouth dissolving drug delivery systems has number of advantage viz., faster onset of action, elegance, ease of administration, ease of manufacturing, ease of storage and transport. A novel attempt has been made to develop mouth dissolving tablets of Ondansetron hydrochloride by including clove oil as flavor and local anesthetic on taste buds. The tablets were prepared by direct compression technique. The formulated tablets were evaluated for Pre formulation and post formulation parameters and they were found to be saatisfactory. Direct compression method was employed for making mouth dissolving tablets. The formulated mouth dissolving tablets possessed good drug releasing property, good mouth feel and improved drug availability with better patient compliance.