ABSTRACT
Abstract Ramipril being ACE inhibitor belongs to BCS class II drug with low solubility and undergoes first-pass metabolism that leads to reduced bioavailability of 28%. The current research is aimed at formulating and evaluating ramipril fast dissolving oral films (FDOF). Solubility enhancement of ramipril was done by formation of inclusion complex with β-cyclodextrin in 3 ratios (1:0.5, 1:1, 1:2). Based on higher drug content and dissolution values the physical mixture of ramipril with β-cyclodextrin in 1:1 ratio (IC2) was chosen for further studies. Total 12 formulations of ramipril FDOF containing IC2 prepared with various polymers and evaluated for physicochemical properties. The optimized formulation F9 shown better tensile strength (11.6 g/cm2), significant % elongation (9.8) and maximum % drug content of 99.98 %. The formulation F9 exhibited minimum disintegration time of 9 sec that is desirable for immediate onset of action and maximum drug release. The FTIR data of F9 assured the compatibility of drug and formulation excipients, found to be stable for 180 days at accelerated conditions. The study confirmed that ramipril FDOF lead to quicker onset of action and enhanced therapeutic efficiency in comparison to marketed product.
ABSTRACT
Diacerein (Diacetylrhein, DCN) is anthraquinone derivatives used in the curing of osteoarthritis, but its usage isrestricted due to its very poor solubility and wettability which result in bioavailability variation. The objective ofthis work was to design fast dissolving tablets (FDTs) of DCN solid dispersion. Solid dispersions (SDs) and physicalmixtures (PMs) were prepared with PEG4000, Polyvinylpyrolidone K25 (PVPK25), and Sorbitol. SD formationincreased the dissolution rate of DCN compared to PM; this demonstrates that the improvement of dissolution ratewith SD can be due to physical change in drug crystal which was confirmed by thermal analysis. SD with Sorbitol wasselected for the preparations of FDTs. Seven formulations were prepared by direct compression method using differentconcentrations of crospovidone (CP) as superdisintegrant and camphor as subliming agent. Pre- and post-compressionevaluation were carried for powder blend and the prepared FDTs, respectively. F7 (composed of 120 mg CP, 45 mgcamphor, 200 mg SD containing 50 mg DCN, 7.5 mg aspartame, 2.5 mg menthol, 2.5 mg Magnesium stearate, and22.5 mg lactose) showed the shortest disintegration time and the highest dissolution rate and it was selected for furtherinvestigation. Kinetic studies of the in vitro release results showed that F7 followed first-order kinetics. Stabilitystudies conducted for formula F7 showed good stability upon storage at 30oC/75% RH and 40oC/75% RH for 12 weeks.
ABSTRACT
The utilization of electrospinning in drug delivery has thrived in recent years, with the ability to incorporate drugsand enhance dissolution; this technique is employed to improve the dissolution of poorly water-soluble selectivephosphodiesterase-5 inhibitor, tadalafil. The strategy involved direct electrospinning of tadalafil/polyvinylpyrrolidoneand polyethylene oxide (PEO) solution. The optimization process included a 32 full factorial design based on theinfluence of polymers concentration as independent variables on the electrospun yield, loading efficiency, nanofibersdiameter, number of beads, and in vitro release. Optimization studies revealed the negative influence of bothpolymers on the electrospun yield, while the loading efficiency and in vitro dissolution rate were reduced by the PEOconcentration solely. The higher polymer concentrations were favorable for the declination of beads number, and adriving factor for fiber diameter reduction. Further physicochemical characterization of the optimized formulationrevealed the presence of the drug in an amorphous state or molecular dispersion within the polymer matrix. In vitrodissolution studies revealed about 81.5% ± 8.34% release in less than 2 minutes compared to a negligible dissolutionof free drug. From the derived outcomes, the electrohydrodynamic spun tadalafil-loaded nanofibers pave the way fordissolution enhancement for insoluble low bioavailability class II drugs.
ABSTRACT
Objective: The main aim of the present research work was to formulate fast dissolving tablets of famotidine by direct compression method and to evaluate the effect of synthetic super disintegrating agent on drug release pattern. Methods: The fast dissolving tablets were prepared by using crospovidone, croscarmellose sodium, sodium starch glycolate as superdisintegrants (2, 4 and 6 %w/w), mannitol 20 % and microcrystalline cellulose (44, 46 and 48 % w/w) as a directly compressible vehicle. All the prepared tablets were evaluated for hardness, friability, drug content uniformity, weight variation, disintegrating time, wetting time and in vitro drug release studies. Results: All the prepared fast dissolving tablets formulations were within the Pharmacopoeial standards limits. Based on in vitro drug release studies (>90 % within 30 min), the optimised formulations were optimised tested for the short term stability (at 40 ˚C/75% RH for 3 mo) and drug excipient interaction (fourier transform infrared spectroscopy). Conclusion: Hence, formulation prepared with 6 % w/w of crosspovidine and 44 % w/w of microcrystalline cellulose as emerged as the overall best formulation (>90 % within 30 min) compared to marketed product (>70 % within 30 min). Short-term stability studies on the formulations indicated that there are no significant changes in drug content and in vitro drug release (p<0.05).
ABSTRACT
Flurbiprofen belongs to Biopharmaceutical Classification System (BCS) class II drugs which are poorly soluble in water. The objective of present research work was to prepare fast dissolving tablets of Flurbiprofen using varying concentrations of three different sublimating agents to improve the dissolution rate. Seven formulations were prepared containing different concentrations of camphor, ammonium bicarbonate and thymol as sublimating agent along with primogel as a superdisintegrant. Tablets were manufactured by direct compression method. The prepared tablets were evaluated for pre-compression and post-compression parameters result, For all formulations result was within official limits. FTIR studies revealed that there were no interactions between the drug and the excipients used. From in vitro drug release studies it was concluded that the formulations F6 and F7 containing 10% and 15% of thymol showed fast drug release of 100.00% and 100.84% respectively in 30 minutes. Formulations containing camphor (F2 & F3) and ammonium bicarbonate (F4 & F5) as sublimating agents showed a drug release of less than 80%, while the control formulation F1 having no sublimating agent showed 49.14% of drug release in 30 minutes. Thus thymol can successfully be used to formulate fast dissolving tablets of flurbiprofen by sublimation method with much better dissolution profile
Subject(s)
Tablets/pharmacology , In Vitro Techniques , Flurbiprofen/analysis , Dissolution/analysis , Drug LiberationABSTRACT
OBJECTIVE: To prepare and optimize meloxicam nanosuspensions fast dissolving sublingual films (MLX-NS-FDSFs) and to evaluate its in vitro dissolution characteristics. METHODS: Meloxicam nanosuspensions (MLX-NS) were prepared by pH-dependent dissolving-precipitating/high speed shearing method and then transformed into fast dissolving sublingual films (FDSFs). The formulations of MLX-NS-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amount of HPMC-E30, PEG-400 and MLX-NS as investigation factors, and particle size of reconstituted nanoparticles from MLX-NS-FDSFs, disintegration time and stretch length as indexes. The morphology, content uniformity and in vitro dissolution of the optimal formulation were also evaluated. RESULTS: The MLX-NS-FDSFs prepared by optimized formulation (35 mg·mL-1 HPMC-E30, 40 mg·mL-1 PEG-400, 10 mL MLX-NS) could fast disintegrate in (26.08±1.76) s, the tensile length was (1.51±0.13) mm, and the particle size of reconstituted nanoparticles from MLX-NS-FDSFs was (186.4±6.3) nm. There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. Morphological analysis showed that well-dispersed MLX nanoparticles embedded in MLX-NS-FDSFs. The conformity of drug content was up to standard. MLX could be released in vitro as much as (91.75±8.05)% within five minutes. CONCLUSION: Using Box-Behnken design and response surface method to optimize MLX-NS-FDSFs is effective and feasible. MLX-NS-FDSFs can significantly increase the cumulative dissolution of MLX.
ABSTRACT
The orally disintegrating tablets(ODT)are the kinds of novel oral dosage forms which begin to gain popularity and acceptance since they can disintegrate/dissolve quickly in the oral cavity upon contact with saliva ,resulting in solutions or suspensions form of the administered medicine. The ODTs are perfect alternative for pediatric and geriatric patients with difficulty in swallowing , and uncooperative patients because of their convenience of self-administration and compactness. This communication reviews the appli?cations and technologies involved in formulation feature,lyophillization process,excipients selection,fast dissolving mechanism,and determination of disintegration time.
ABSTRACT
The orally disintegrating tablets (ODT) are the kinds of novel oral dosage forms which begin to gain popularity and acceptance since they can disintegrate/dissolve quickly in the oral cavity upon contact with saliva, resulting in solutions or suspensions form of the administered medicine. The ODTs are perfect alternative for pediatric and geriatric patients with difficulty in swallowing, and uncooperative patients because of their convenience of self-administration and compactness. This communication reviews the applications and technologies involved in formulation feature, lyophillization process, excipients selection, fast dissolving mechanism, and determination of disintegration time.
ABSTRACT
The present study was aimed to formulate, develop and evaluate the fast dissolving tablets of diclofenac sodium, used for the treatment of arthritis, inflammation, pain. Fast dissolving tablets of diclofenac sodium were prepared by direct compression method using crospovidone and sodium starch glycolate as superdisintegrants in concentrations of 5.3%, 6.6% and 8% w/w and in combination. In this work microcrystalline cellulose and mannitol are investigated as diluents. Prepared powder mixtures were evaluated for drug excipient compatibility with FTIR spectroscopy and DSC analysis. Prepared formulations are evaluated for In vitro dissolution, disintegration dispersion and wetting time. Formulation FCS6 prepared with combination of crospovidone and sodium starch glycolate at weight ratio of 6.6 and 2.3% showed better results compare with control. Post compression parameters like hardness (3.4 kg/cm2) and friability (0.31%) are at good acceptable levels in accordance with official compendia. FCS6 showed improved dissolution (99.8 %) and dispersion (75 seconds) profiles compared to control. The FTIR and DSC showed no interaction between the drug and excipients. The optimized formula FCS6 showed good drug release characteristics with acceptable mouth feel and fast dissolving properties.
ABSTRACT
The environment of oral cavity provides a large surface area for the delivery of drugs bypassing the first pass metabolism in the liver. Hence, the oral cavity is being targeted for providing quicker delivery of drugs for immediate action. However, oral delivery system in the form of tablets/ capsules needs modifications in elderly, children, and unconscious patients because of the fear of choking and aspiration. To overcome these problems much research is being undertaken to develop oral bio dissolving films as an alternative to tablets. The objective of the article was to provide an overview of the composition, advantages and disadvantages, and uses of bio dissolving films in the field of medicine and dentistry.
Subject(s)
Administration, Oral , Airway Obstruction/prevention & control , Biofilms/classification , Coated Materials, Biocompatible , Dentistry/drug therapy , Dentistry/therapy , Drug Delivery Systems , Humans , Pharmaceutical Preparations, Dental/administration & dosage , PolyvinylsABSTRACT
Novel drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and bio-chemical parameters pertinent to their performance. Despite tremendous advancements in drug delivery, the oral route remains the perfect route for the administration. Novel drug delivery system assists to achieve better patient compliance. Fast dissolving tablets are one of them.FDT have benefits such as accurate dosing, easy portability and manufacturing, good physical and chemical stability and an ideal alternative for pediatric and geriatric patients. FDDT formulation combines the advantage of both liquid and conventional tablet formulation while also offering advantage over both traditional dosage forms. 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.
ABSTRACT
Recent developments in technology have presented viable dosage alternatives for patients who may have difficulty swallowing tablets or liquids. Traditional tablets and capsules administered with an 8-oz. glass of water may be inconvenient or impractical for some patients. For example, a very elderly patient may not be able to swallow a daily dose of antidepressant. An eight-year-old with allergies could use a more convenient dosage form than antihistamine syrup. A schizophrenic patient in the institutional setting can hide a conventional tablet under his or her tongue to avoid their daily dose of an atypical antipsychotic. A middle-aged woman undergoing radiation therapy for breast cancer may be too nauseous to swallow her H2-blocker. The convenience of administration and improved patient compliance are important in the design of oral drug delivery system which remains the preferred route of drug delivery inspite of various disadvantages. One such problem can be solved in the novel drug delivery system by formulating “mouth dissolving tablets” (MDTs) which disintegrates or dissolves rapidly without water within few seconds in the mouth due to the action of super-disintegrant or maximizing pore structure in the formulation. The review describes the various formulation aspects, technologies developed for MDTs, marketed formulation and drugs used in this research area.
ABSTRACT
Objective: To prepare and optimize glycyrrhizic acid bile salt/phosphatidylcholine mixed-micelles fast dissolving sublingual films (GL-BS/PC-MM-FDSFs) and preliminarily evaluate its mucous membrane permeation in vitro. Methods: The formulations of GL-BS/PC-MM-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amounts of sodium alginate, propylene glycol, and GL-BS/PC-MM as investigation factors, and the disintegration time, cumulative release of drug from the GL-BS/PC-MM-FDSFs within 5 min, and particle size of reconstituted MM from GL-BS/PC-MM-FDSFs as indexes. Mucous membrane permeation test was evaluated in vitro with porcine sublingual mucosa as a model by using Franz diffusion cell. Results: The GL-BS/PC-MM-FDSFs prepared by optimized formulation (23 g/L sodium alginate, 148.5 g/L propylene glycol, and 7.58 mL GL-BS/PC-MM) could fast disintegrate in (22.1 ± 0.7) s, release in vitro at 5 min to (85.30 ± 2.91)%, and the particle size of reconstituted MM from GL-BS/PC-MM-FDSFs was obtained as (146.46 ± 6.42) nm. There was a little deviation between the theoretically predicted value and measured value. It showed that this model had a good prediction. There was no significant difference between the accumulative permeation profiles of GL-BS/PC-MM-FDSFs and GL-BS/PC-MM at each time point. Conclusion: The process that GL-BS/PC-MM is solidified to GL-BS/PC-MM-FDSFs is simple and feasible, and GL-BS/PC- MM-FDSFs could significantly improve the mucous membrane absorption of GL.
ABSTRACT
The main aim of the present research was to develop a fast dissolving oral polymeric film with good mechanical properties, faster disintegration and dissolution when placed on tongue. Donepezil hydrochloride (DPH) is prescribed in the treatment of mild to moderate Alzheimer’s disease (AD). The polymers selected for preparing films were sodium alginate (SA), poly vinyl alcohol (PVA) and guar gum (GG). Three batches of films were prepared by solvent casting method with sodium alginate, sodium alginate & PVA and with the combination of sodium alginate & guar gum. From these three batches, three optimized film formulations S3, SP7 and SG8 were selected based on disintegration time. To these three selected film formulations, superdisintegrants sodium starch glycolate (SSG), cross carmellose sodium (CCS) and cross povidone (CP) were added at a concentration of 4% w/w of polymer to improve the disintegration time. The films prepared with or without superdisintegrants were compared for fast releasing properties. Based on DT and in vitro dissolution data, S3CP was selected as the best formulation among the all formulations.
ABSTRACT
Taste masking becomes a pre-requisite for bitter drugs to improve the patient compliance especially in the pediatric and geriatric population. Metoclopramide hydrochloride is recommended in dose of 10 to 15 mg four times a day for getting relief from nausea, vomiting, stomach pain and reflux oesophagitis. It finds application in all the categories of patients.In the present study an attempt has been made to prepare bitterless fast dissolving tablet of Metoclopramide Hydrochloride using stevia leaf powder as a taste masking agent. Direct compression was the technique used for preparing taste masked tablets.
ABSTRACT
The main aim of the present research was to develop a fast dissolving oral polymeric film with good mechanical properties, faster disintegration and dissolution when placed on tongue. Donepezil hydrochloride (DPH) is prescribed in the treatment of mild to moderate Alzheimer’s disease (AD). The polymers selected for preparing films were sodium alginate (SA), poly vinyl alcohol (PVA) and guar gum (GG). Three batches of films were prepared by solvent casting method with sodium alginate, sodium alginate & PVA and with the combination of sodium alginate & guar gum. From these three batches, three optimized film formulations S3, SP7 and SG8 were selected based on disintegration time. To these three selected film formulations, superdisintegrants sodium starch glycolate (SSG), cross carmellose sodium (CCS) and cross povidone (CP) were added at a concentration of 4% w/w of polymer to improve the disintegration time. The films prepared with or without superdisintegrants were compared for fast releasing properties. Based on DT and in vitro dissolution data, S3CP was selected as the best formulation among the all formulations.
ABSTRACT
The demand for fast dissolving tablets has been growing during the last decade, especially for elderly and children who have swallowing difficulties. In the present work, fast dissolving tablets of metoprolol tartrate, were prepared using sodium starch glycolate, sodium croscarmellose and crospovidone as superdisintegrants, by the direct compression method. The tablets prepared were evaluated for various parameters including weight variation, hardness, friability, in vitro dispersion time, drug-polymer interaction, drug content water absorption ratio, wetting time, in vitro drug release, FTIR and DSC studies. The tablets prepared by the direct compression method had a weight variation in the range of 145 mg to 152 mg, which is below ± 7.5%, a hardness of 3.6 kg/cm² to 4.5 kg/cm², percentage friability of 0.46% to 0.73%, in vitro dispersion time of 18 s to 125 s, drug content uniformity of between 98.12% and 100.03%, a water absorption ratio of 67% to 87%, wetting time of 32 sec. to 64 sec., and an in vitro drug release of 53.92% - 98.82% within 15 min. The IR spectral analysis and DSC study showed no drug interaction with formulation additives of the tablet, and the formulations indicated no significant changes in hardness, friability, drug content or in vitro drug release. Fast dissolving tablets of metoprolol tartrate have enhanced dissolution and will lead to improved bioavailability and more effective therapy.
A exigência por comprimidos de dissolução rápida aumentou durante a última década, especialmente para idosos e crianças, com dificuldades de deglutição . No presente trabalho prepararam-se, pelo método de compressão direta, comprimidos de tartarato de metoprolol de rápida dissolução, utilizando glicolato sódico de amido, croscarmellose sódica e crospovidona como superdisintegrantes. Os comprimidos preparados foram avaliados em relação a diferentes parâmetros, como variação de peso, dureza, friabilidade, tempo de dispersão in vitro, interação fármaco-polímero, taxa de absorção de água pelo fármaco, tempo de umedecimento, liberação do fármaco in vitro,, FTIR e estudos de DSC. Os comprimidos preparados por compressão direta apresentaram variação de peso de 145 mg a 152 mg, abaixo de ±7,5%, dureza de 3,6 kg/cm² a 4,5 kg/cm² , porcentagem de friabilidade de 0,46% a 0,73%, tempo de dispersão in vitro de 18 s a 125 s, uniformidade de conteúdo de fármaco entre 98,12% e 100,03%, taxa de absorção de água de 67% a 87%, tempo de umidificaçãode 32 s a 64 s liberação do fármaco in vitro entre 53,92% e 98,82%, em 15 min. A análise no IV e de DSC mostrou que não houve interação de fármacos com os aditivos de formulação do comprimido e as formulações indicaram que não houve mudança significativa na dureza, friabilidade, s uniformidade de conteúdo de fármaco e na liberação do fármaco in vitro. Os comprimidos de liberação rápida apresentaram aumento na dissolução de tartarato metoprolol e conduzem à melhoria dabiodisponibilidade e à terapia eficaz.
Subject(s)
Tablets/analysis , Tartrates/pharmacokinetics , In Vitro Techniques/classification , Dissolution/classification , Deglutition , GlycolatesABSTRACT
Levofloxacin hemihydrate is an antibiotic used for bacterial infections. It belongs to flouroquinolones class. Fast dissolving tablets gaining popularity over conventional tablets due to their convenience in administration and suitability for patients like geriatrics and pediatric patients because of their swallowing difficulties. The half-life of the drug is 6-8 hrs and it is rapidly and completely absorbed after oral use for that levofloxacin prepared as fast dissolving tablets. Tablets were prepared by direct compression technique by using MCC as binder. Super disintegrants used are SSG(2%,3%,4% and 5%),CCS(AC-DI-SOL) (2%,3%,4%and 5%), CP(2%,3%,4%and5%)and FGP(2%,3%,4%and 5%),.Among these 4 super disintegrants, Fenugreek powder (FGP) was show best results in the evaluation tests.
ABSTRACT
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.
Subject(s)
Tablets/analysis , Nifedipine/analysis , /classification , Chemistry, Pharmaceutical/methods , beta-Cyclodextrins/analysis , Solubility , Dissolution/classificationABSTRACT
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 dissolving tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. 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. This review describes the various formulation aspects, disintegrants employed and technologies developed for FDTs, patent formulation, evaluation tests, and marketed formulations.