Development and evaluation of the tablets coated with the novel formulation termed thin-layer sugarless coated tablets

The purpose of this study was to develop and evaluate the thin-layer sugarless coated tablets containing Vitamin C, Vitamin E, Vitamin B2, calcium pantothenate, and L-cysteine. As a result of the formulation study, three coating layers, 2% under coating (UC), 38% build-up coating (BC), and 5% syrup coating (SC) were necessary for sufficient impact toughness, elegant appearance, and improvement of appearance stability after storage at 25 degrees C/75% RH for 6 months under open conditions. We demonstrated that the thin-layer sugarless coated tablets are superior to the sugar-coated tablets in terms of small tablet size and stability of calcium pantothenate. It was due to the coating method, the continuous spray mist method, which can minimize the thicknesses of coating layers and the moisture content in the tablets. We also demonstrated that the thin-layer sugarless coated tablets are superior to the film-coated tablets in terms of masking ability of the unpleasant odor and the appearance, stability of the appearance, and low hygroscopicity. It was due to the dense, opaque, and stable coating layers mainly consist of erythritol. We revealed that thin-layer sugarless coated tablets have both advantages of film-coated tablets and sugar-coated tablets.     

Characteristics of erythritol and formulation of a novel coating with erythritol termed thin-layer sugarless coating

The purpose of this study was to clarify the characteristics of erythritol and to develop the optimum basic formulation of a novel coating with erythritol termed thin-layer sugarless coating. Characteristics of erythritol were investigated compared with maltitol, mannitol, sorbitol, xylitol, and sucrose. Furthermore, the optimum basic formulation of thin-layer sugarless coating with erythritol was determined by coating glass beads. We selected a continuous spray mist method for thin-layer sugarless coating due to the formation of a thin sugarless coating layer by a simple method. We demonstrated that erythritol is a suitable coating material for thin-layer sugarless coating compared with maltitol, mannitol, sorbitol, xylitol, and sucrose because of its high water solubility, low hygroscopicity, instant crystallization, and low tackiness. We also demonstrated that thin-layer sugarless coating with erythritol can reduce coating time compared with the coating with maltitol or sucrose due to its characteristics. We developed the optimum basic formulation of thin-layer sugarless coating consists of erythritol, powdered acacia, and talc. We confirmed that a smooth coating layer and high coating efficiency were achieved using the formulation.     

Structural and in vitro in vivo evaluation for taste masking

ABSTRACT

Introduction: Although many techniques, such as complexation and microencapsulation, are used to mask the unpleasant taste of drugs, the success of all masking processes is evaluated in the same way. To evaluate the success of a masking process, a masked formulation must pass two tests: a structural test and an in vitro in vivo test.

Areas covered: This review article highlights structural evaluation and in vitro in vivo evaluation of a taste-masking process. The structural evaluation has two criteria: the absence of any chemical interaction between the drug and the masking agent and the molecular distribution of drug in the network of masking agent. The in vitro in vivo section can be verified by electronic tongues, dissolution test, and volunteers and it should confirm that the final product, after applying the masking process, will have a lower rank in terms of taste.

Expert opinion: This critical review helps researchers and industrial partners to evaluate a taste-masking process in a systematic way, leading to better understanding of taste-masking process and consequently improving the efficiency of masked dosage forms while hindering the unpleasant taste of drugs. This will ultimately improve the quality of life of many patients.     

An investigation into the in vivo performance variability of pH responsive polymers for ileo-colonic drug delivery using gamma scintigraphy in humans

Gastrointestinal performance of tablets coated with pH responsive acrylic polymers (Eudragit) was investigated in human volunteers. Tablet cores were coated with Eudragit S dissolved in ethanol (organic), Eudragit S aqueous dispersion (aqueous), or Eudragit FS aqueous dispersion. Eight fasted volunteers received the tablets in a two-way crossover design-treatment 1: Eudragit S (organic) and Eudragit FS coated tablets; treatment 2: Eudragit S (aqueous) and Eudragit FS coated tablets. Eudragit FS coated tablets were included in both treatments to assess its intra-subject performance. Tablets were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded. Tablets coated with Eudragit S (aqueous) disintegrated in all volunteers mainly in the proximal to mid small intestine. Eudragit S (organic) tablets failed to disintegrate in three out of eight volunteers, while disintegration was in the ileo-caecal junction and ascending colon in all others. Eudragit FS coated tablets disintegrated in 14 out of the 16 administrations. The Eudragit FS coated tablets that did disintegrate exhibited consistent intra- and inter-subject performance, with the site of disintegration focused on the ileo-caecal junction and ascending colon. These in vivo results correlate better with our published in vitro dissolution data in physiological bicarbonate buffers compared to phosphate buffers.     

Preparation and evaluation of taste masked orally disintegrating tablets with granules made by the wet granulation method

Using furosemide (FU) as a model drug, we examined the wet granulation method as a way to improve the taste masking and physical characteristics of orally disintegrating tablets (ODTs). In the wet granulation method, yogurt powder (YO) was used as a corrective and maltitol (MA) was used as a binding agent. The taste masked FU tablets were prepared using the direct compression method. Microcrystalline cellulose (Avicel? PH-302) and mannitol were added as excipients at a mixing ratio of 1/1 by weight. Based on the results of sensory test on taste, the prepared granules markedly improved the taste of FU, and a sufficient masking effect was obtained at the YO/FU ratio of 1 or more. Furthermore, it was found that the masking effect achieved by YO granules made with the wet granulation method was similar to or better than that produced by the granules made with dry granulation method. All types of tablets displayed sufficient hardness (over 3.5×10(-2) kN), and rapidly disintegrating tablets were obtained with YO granules produced at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s. Disintegration time lengthened as the mixing ratio of YO to FU increased. In the mixing ratio of FU/YO=1/1, the hardness of tablets with granules made by the wet granulation method exceeded that of tablets with granules made by the dry granulation method, with minimal differences in disintegration time. The hardness and disintegration time of the tablets with granules made by the wet granulation method could be controlled by varying the compression force. In conclusion, YO was found to be a useful additive for masking unpleasant tastes. FU ODTs with improved taste, rapid disintegration and greater hardness could be prepared with YO-containing granules made by the wet granulation method using MA as a binding agent.     

Enhancement of the Aqueous Solubility and Masking the Bitter Taste of Famotidine Using Drug/SBE-β-CyD/Povidone K30 Complexation Approach

The objective of the present study was to evaluate the potential of ternary system (comprised of famotidine, β-cyclodextrin (β-CyD) or its derivatives and a hydrophilic polymer) as an approach for enhancing the aqueous solubility and masking the bitter taste of famotidine. The aqueous solubility of famotidine increased in the presence of β-CyDs, particularly sulfobutyl ether β-CyD (SBE-β-CyD), and it was further enhanced by the combination of SBE-β-CyD and polyvinyl pyrrolidone (Povidone) K30. The solid binary (drug-β-CyDs) and ternary (drug-β-CyDs-Povidone K30) systems were prepared by the kneading and freeze-drying methods. The dissolution rates of these solid systems were much faster than that of the drug alone. A taste perception study was carried out, initially using a taste sensory machine and subsequently on human volunteers to evaluate the taste masking ability of the ternary complexation. Our results indicated that the combination of SBE-b-CyD and Povidone K30 is effective not only in the enhancement of the solubility and dissolution rate of famotidine, but also in masking of the bitter taste of the drug. This technique may be of value for the pharmaceutical industries, especially in preparation of rapidly disintegrating tablets dealing with bitter drugs to improve patient compliance and thus effective pharmacotherapy.     

Formulation, evaluation and pharmacokinetics of colon targeted pulsatile system of flurbiprofen

Objective: The intent of the present investigation is to develop colon targeted compression coated flurbiprofen pulsatile release tablets that retard the drug release in the upper gastro intestinal system but progressively release in the colon. Materials and methods: Flurbiprofen core tablets were prepared by direct compression method and were compression coated with hydroxypropyl methylcellulose and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. Results and discussions: The optimized formulation showed negligible drug release (7.26?±?0.05%) in the initial lag period followed by progressive release (99.27?±?0.46%) for 24?h. The X-ray imaging study in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C(max) of colon targeted tablets was 10792.62?ng/mL at T(max) 10?h where as in case of immediate release tablets the C(max) was 15684.79?ng/mL at T(max) 3?h signifies the ability of compression coated tablets to target the colon. Conclusion: Development of pulsatile release compression coated tablets using combination of time dependent and pH sensitive approaches was suitable to target the flurbiprofen to colon.     

基于电子鼻技术区分不同产地的牡丹皮药材

目的 应用电子鼻技术区分不同产地的牡丹皮药材。方法 通过单因素及正交试验法确定牡丹皮药材电子鼻测定的最佳试验条件。应用Loading分析法对传感器区分样品的能力进行分析,应用主成分分析法、线性判别分析法来区分不同产地的牡丹皮药材。结果 电子鼻技术测定牡丹皮药材的最佳试验条件为称样量3.0 g,空气流速300 mL·min^-1,样品室温放置时间为10 min;研究结果表明,其区分度均>0.980;7号传感器W1W对第一主成分贡献率最大,2号传感器W5S对第二主成分贡献率最大。通过对牡丹皮药材进行气味识别,电子鼻技术对亳州、铜陵、重庆3个主产区的牡丹皮药材有一定的区分能力,亳州产区不同产地之间区分度不明显。结论 利用牡丹皮药材特殊的气味并运用电子鼻对不同产地的牡丹皮药材进行区分,效果显著,为快速、简便的鉴别不同产地的牡丹皮药材提供新思路。     

口服固体制剂掩味技术的研究进展

综述各种新兴口服固体制剂掩味技术的原理、特点及制备过程,并简述口服掩味技术评价方法的最新进展。口服固体制剂中许多药物由于受到不良口味的影响,致使病人的用药顺应性差、临床应用受限。近年来在使用矫味剂、麻痹剂等掩味手段的基础上产生了许多新兴的掩味技术,如喷动床包衣、粉末包衣和盐析包衣等。     

Evaluation of an enteric coated naproxen tablet using gamma scintigraphy and pH monitoring

Enteric coated naproxen tablets and pH-sensitive radiotelemetry capsules were both radiolabelled and administered to 6 healthy volunteers following breakfast. The median gastric emptying times for the tablets and capsules were 3.3 h and 4.2 h, respectively. In general, the intragastric pH remained below 2 with only transient increases following food consumption. Five of the naproxen tablets disintegrated in the small intestine and one in the stomach. In the ileum the pH was greater than 6 resulting in a mean time for tablet disintegration of 1.2 h after gastric emptying. There was a close correlation between tablet disintegration and the first detection of naproxen in the blood. Peak plasma concentrations of the drug occurred 4 h after tablet disintegration. This study has demonstrated that gastric emptying is the main factor influencing the onset of drug release from enteric coated tablets.     

Practical approaches of taste masking technologies in oral solid forms

In the pharmaceutical industry, taste masking techniques are applied to prevent active pharmaceutical ingredients exhibiting a bitter and unpleasant taste. The oral administration of bitter drugs through solid dosage forms requires an acceptable degree of palatability, patient tolerance and significant therapeutic value. In the recent years, enormous progress in taste masking technologies has given rise to novel strategies such as fast dissolving dosage forms, chewable tablets and coating of molten materials. Similarly, common technologies applying double coating layers, microencapsulation or even chemical modification have been employed to improve patient compliance. This review endeavours to present the practical technologies and platforms applied for taste masking and indicate the most interesting features of each approach.     

基于苦味产生机制的掩味策略与评价

口服制剂中许多药物尤其是中药常常会由于不良口味的影响,致使患者的顺应性降低,限制了临床应用。文章以苦味产生机制为主线,综述目前药物掩味技术的原理、特点和制备过程,并简述掩味技术评价方法的最新进展。     

Formulation and development of release modulated colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer

The objective of the present study was to develop a colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer. Efficacy of selective cyclooxygenase-2 inhibitors has been proven in colorectal cancer. Meloxicam is a selective cyclooxygenase-2 inhibitor with pH-dependent solubility. To achieve pH-independent drug release of meloxicam, pH modifying agents (buffering agents) were used. Meloxicam tablets containing polyethylene oxide were dually coated with ethyl cellulose containing hydrophilic material, polyethylene glycol as an inner coating layer and methyl acrylate, methyl methacrylate, and methacrylic acid copolymer (Eudragit? FS 30D) as outer coating layer for colon targeting. Optimized tablet formulations demonstrated good potential to deliver the drug to the colon by successfully exhibiting a lag time of 5?h during in vitro drug release study. An in vivo evaluation study conducted to ascertain pharmacokinetic parameters in rabbits revealed that the onset of drug absorption from the coated tablets (T(lag time)?=?4.67?±?0.58?h) was significantly delayed compared to that from the uncoated tablets. The AUC(0→)(t) and AUC(0→∞) for coated tablets were lower than of uncoated tablets, although the difference was not significant (p?>?0.01). The roentgenography study revealed that the tablet remained intact, until it reached the colon (5?h), which demonstrates that the system can efficiently deliver the drug to the colon. This study demonstrated that a meloxicam-loaded colon targeted system exhibited promising targeting and hence may be used for prophylaxis of colorectal cancer.     

Demonstration of pharmaceutical tablet coating process by injection molding technology

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300?μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.     

Formulation,evaluation and pharmacokinetics of colon targeted pulsatile system of flurbiprofen

Objective: The intent of the present investigation is to develop colon targeted compression coated flurbiprofen pulsatile release tablets that retard the drug release in the upper gastro intestinal system but progressively release in the colon.

Materials and methods: Flurbiprofen core tablets were prepared by direct compression method and were compression coated with hydroxypropyl methylcellulose and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery.

Results and discussions: The optimized formulation showed negligible drug release (7.26?±?0.05%) in the initial lag period followed by progressive release (99.27?±?0.46%) for 24?h. The X-ray imaging study in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C_max of colon targeted tablets was 10792.62?ng/mL at T_max 10?h where as in case of immediate release tablets the C_max was 15684.79?ng/mL at T_max 3?h signifies the ability of compression coated tablets to target the colon.

Conclusion: Development of pulsatile release compression coated tablets using combination of time dependent and pH sensitive approaches was suitable to target the flurbiprofen to colon.     

Taste masking of paracetamol by hot-melt extrusion: An in vitro and in vivo evaluation

The purpose of this study was the in vitro and in vivo evaluation of the masking efficiency of hot melt extruded paracetamol (PMOL) formulations. Extruded granules containing high PMOL loadings in Eudragit EPO® (EPO) or Kollidon® VA64 (VA64) were prepared by hot-melt extrusion (HME). The taste masking effect of the processed formulation was evaluated in vivo by a panel of six healthy human volunteers. In addition, in vitro evaluation was carried out by an Astree e-tongue equipped with seven sensors. Taste sensing technology demonstrated taste improvement for both polymers by correlating the data obtained for the placebo polymers and the pure APIs alone. The best masking effect was observed for VA64 at 30% PMOL loading. The e-tongue results were in good agreement with the in vivo evaluation. In vitro dissolution of the extruded granules showed rapid PMOL releases.     

Taste masked microspheres of ofloxacin: formulation and evaluation of orodispersible tablets

Ofloxacin is a synthetic chemotherapeutic antibiotic used for treatment of a variety of bacterial infections, but therapy suffers from low patients' compliance due to its unpleasant taste. This study was aimed to develop taste masked microspheres of ofloxacin using Eudragit and to prepare orodispersible tablets of the formulated microspheres using natural superdisintegrant. Taste masking Eudragit E100 microspheres were prepared by solvent evaporation technique with an entrapment efficiency ranging from 69.54 ± 1.98 to 86.52 ± 2.25%. DSC revealed no interaction between the drug and polymer. Microspheres prepared at a drug/polymer ratio of 1:4 and 1:5 revealed sufficient flow properties and better taste masking as compared to other ratios. Drug loaded microspheres were formulated as orodispersible tablets using locust bean gum as a natural superdisintegrant offering the advatages of biocompatibility and biodegrad-ability. The wetting time, water absorption ratio and in-vitro disintegration time of the tablets were found to range between 19 ± 2 to 10 ± 3 seconds, 59.11 ± 0.65 to 85.76 ± 0.96 and 22 ± 2 to 10 ± 2 seconds, respectively. The in-vitro ofloxacin release was about 97.25% within 2h. The results obtained from the study suggested the use of eudragit polymer for preparing ofloxacin loaded microspheres with an aim to mask the bitter taste of the drug and furthermore orodispersible tablets could be formulated using locust bean gum as a natural superdisintegrant.     

Utilization of date syrup as a tablet binder,comparative study

The aim of this study was to investigate the possibility of using dates syrup as a tablet binder. Dates syrup (40%, 50%, 60% w/w dates syrup:water) was utilized for the granulation of sodium bicarbonate and calcium carbonate as examples for water-soluble and water-insoluble materials; correspondingly. Those two materials represent examples of bulky drugs as well. Starch paste (10% w/w starch in water) and sucrose syrup (50% w/w sucrose in water), the well-known tablet binders, were used in the granulation of the same materials for the sake of comparison. The granulations were evaluated with regard to particle size and particle size distribution, granule strength, bulk density, flowability, moisture content and compression behavior. In addition, tablets prepared and evaluated from these granules. Taste and flavor of the prepared tablet have been tested by seven healthy volunteers. Within the scope of this work, dates syrup showed excellent properties as a tablet binder in comparison to starch paste or sucrose syrup for the granulation of both water-soluble and water-insoluble materials. Also, better flavoring and masking taste have been noticed from an evaluation by human volunteers demonstrating the usefulness of the date syrup as sweetener and flavoring the tablets in addition to its use as binder.     

Bioavailability of a valproic acid preparation. The relative bioavailability of enteric-resistant valproic acid preparations in tablet form with simultaneously administered tetradeuterated valproic acid as the bioavailability reference

The relative bioavailability was measured for the 150-, 300-, and 600-mg enteric coated Leptilan tablets (valproic acid, sodium salt) using a new method. Simultaneously an equimolar amount of a tetradeuterated valproic acid - di-(2,3-dideutero-n-propyl)-acetic acid - was given as an aqueous solution of the sodium salt. This methodology excludes effects on the two partial pharmacokinetics caused by time-dependent intraindividual variations of the metabolising capacity or other biochemical or physiological changes in the body of the volunteer. Therefore, this methodology gives already reliable data for bioavailability when using only small numbers of volunteers. The relative bioavailability of the enteric coated Leptilan tablets was 95.5 +/- 0.6%, 104.4 +/- 7.6%, and 100.7 +/- 2.4% (mean from experiments with 3 volunteers each) for the 150-, 300-, and 600-mg tablets respectively.     

A novel powder coating process for attaining taste masking and moisture protective films applied to tablets

A novel powder coating process was developed for the application of taste masking and moisture protective films on tablets while avoiding the use of solvents or water. The coalescence of particles to form a polymeric film was investigated through studies of dry powder layering of micronized acrylic polymer (E PO) to produce free films. Theophylline containing tablets were coated with the same acrylic polymer in a laboratory scale spheronizer using a powder coating technique. The dry powder layer delayed the onset of drug release in pH 6.8 medium, depending on the coating level, while no delay was observed in pH 1.0 medium. The presence of hydrophilic polymers in the acrylic coating layer decreased the lag time for drug release in pH 6.8 medium, while only the presence of HPMC in the film slowed the drug release rate in acidic medium. The dry coating process was demonstrated to be a reliable alternative to solvent or aqueous film coating technologies for applying taste masking and moisture protective film coats onto compressed tablets. A controlled drug release profile was achieved in pH 6.8 media.