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.     

气相色谱法同时测定木糖醇氯化钠注射液中4种多元醇的含量

目的:建立测定木糖醇氯化钠注射液中4种多元醇(L-阿拉伯糖醇,甘露醇,半乳糖醇,山梨醇)的气相色谱(GC)法。方法:以赤藻糖醇为内标,采用毛细管气相色谱法对木糖醇氯化钠注射液中4种多元醇进行含量测定。结果:L-阿拉伯糖醇,甘露醇,半乳糖醇和山梨醇在各自的浓度范围内均具有良好的线性关系(r均为0.999以上);平均回收率(n=9)分别为98.9%～100.5%,101.0%～101.6%,99.0%～102.1%和100.9%～102.4%。结论:本方法简单、结果准确、重现性好,可更好的控制药品质量。     

Suitability of sugar alcohols as antidiabetic supplements: A review

The major goals in the management of diabetes are to maintain optimum control of high blood glucose level or hyperglycemia. Dietary modification is one of the most recommended treatment modalities for diabetic patients. The use of foods sweetened with sugar alcohols (also known as polyols) such as xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt and erythritol has brought an escalating interest in the recent years since some sugar alcohols do not rise plasma glucose, as they are partially digested and metabolised. Diet composition and adequacy may be altered by replacing carbohydrates with sugar alcohols. It has been established that these polyols are appropriate sugar substitutes for a healthy lifestyle and diabetic foods. The present review focuses on the evidence supporting the use of sugar alcohols in the management of diabetes, by evaluating their physical and chemical properties, metabolism, absorption, glycemic and insulinemic responses. Although documentation on the glycaemic and insulinemic response of polyols is evident that these compounds have beneficial effects on the better management of hyperglycemia, the possible side effects associated with their normal or higher dosages warned their use according to the relevant Food & Drug Administration guidelines. For the same reason, future studies should also focus on the possible toxicity and side effects associated with the consumption of sugar alcohols in order to define their safety.     

The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol

The aim of this study was to examine the influence of polyhydric alcohols (taste masking agents) on the rheological properties of in situ gelling pectin formulations and on the in vitro and in vivo release of paracetamol and ambroxol from these formulations. Gelation of orally administered pectin solutions containing calcium in complexed form occurred on release of calcium in the acidic environment of the stomach. Inclusion of 10% (w/v) sorbitol in 2% (w/v) pectin sols reduced the viscosity and ensured Newtonian flow properties. Xylitol and mannitol in similar concentrations were less effective in reducing viscosity; sucrose increased viscosity and caused non-Newtonian flow. The in vitro release of paracetamol from 2% (w/v) pectin gels formulated with 10% (w/v) of sorbitol, erythritol, xylitol or mannitol, and of ambroxol from 2% (w/v) pectin gels containing 10% (w/v) sorbitol, followed diffusion-controlled kinetics. Pectin gels (2%, w/v) containing sorbitol (10%, w/v) sustained the release of paracetamol in the rat stomach and bioavailabilities of approximately 90% of those from an orally administered paracetamol syrup were achieved. Sustained release of ambroxol from in situ gelling formulations was achieved with pectin concentrations of 1.5 and 1% (w/v) and a sorbitol concentration of 10% (w/v).     

Application of an electronic nose system for evaluation of unpleasant odor in coated tablets.

The purpose of this study was to apply an electronic nose system for evaluation of unpleasant odor in tablets containing L-cysteine, an unpleasant odor drug, and demonstrate the odor masking ability of thin-layer sugarless coated tablets, which we have newly developed, by both electronic nose system and sensory evaluations. We demonstrated the qualitative evaluation of the unpleasant odor using air as a reference indicator and the quantitative evaluation of the unpleasant odor using the distances between air and samples in the electronic nose system evaluation. The electronic nose system evaluation was positively and well-correlated with the sensory evaluation by volunteers. We suggest that the electronic nose system evaluation is appropriate as an alternative or a support method for sensory evaluation by volunteers. As the results of both electronic nose system and sensory evaluations, we demonstrated that the thin-layer sugarless coated tablets have excellent masking ability of the unpleasant odor, equivalent to that of sugar-coated tablets due to the dense coating layers.     

Development of directly compressible powders via co-spray drying.

Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility, powder hygroscopicity, flowability, and compactability. The influence of process parameters during spray drying on the compaction behaviour of drug/excipient mixtures was investigated via Heckel analysis. Erythritol, lactose, maltodextrin, and mannitol were efficient in co-spray drying with acetaminophen. However, lactose mixtures showed poor flowability. Spray dried mixtures containing mannitol and erythritol were characterised as non-hygroscopic, highly dense, and good flowing powders. Mannitol increased tablet tensile strength in contrast with the poor compactability of erythritol. Maltodextrin was selected for further experiments because it provided excellent tablet tensile strength. The use of erythritol, maltodextrin and mannitol in binary drug/excipient mixtures resulted in high process yields. Compacts of erythritol, mannitol, and maltodextrin were characterised by higher tablet tensile strength at higher spray drying temperatures due to the increased particle fragmentation of erythritol and mannitol mixtures and to the increased plastic deformation of maltodextrin formulations. A combination of erythritol, maltodextrin, and mannitol was selected for further formulation and process optimisation of co-spray dried powders for direct compression.     

Evaluation of a novel sugar coating method for moisture protective tablets

A novel method of manufacturing one-step dry-coated (OSDRC) tablets, which we recently invented, was used to produce sugar-coated tablets protected from moisture without the need for a conventional complicated sugar coating process. Amorphous sucrose was selected for the outer layer of the OSDRC tablets as sugar-coated layer. The isothermal crystallization behavior and characteristics such as water vapor permeability, tensile strength, and disintegration time of compressed amorphous sucrose were investigated. Water vapor adsorption measurements showed the crystallization behavior of amorphous tablets to be similar to that of amorphous powder, although it was affected by compression pressure. We found that the crystallized amorphous sucrose after compression at 200 MPa was moisture protective, and the water vapor permeability coefficient was decreased to 1/2000 or less compared with a tablet prepared with a lactose-microcrystalline cellulose (MCC) mixture, hydroxypropylmethylcellulose (HPMC), and sucrose crystal. The water vapor permeability and physicochemical characteristics were influenced by the amorphous content or additive content. It was confirmed that a new sugar-coated tablet using amorphous sucrose and OSDRC technology was moisture protective, therefore, it was concluded that the novel sugar coating method was very useful to obtain a moisture protective tablet.     

Alternative sugars as potential carriers for dry powder inhalations

Most dry powder inhaler (DPI) formulations rely on lactose monohydrate as a carrier in the drug powder blends. However, lactose cannot be used for compounds that interact with the reducing sugar function of the lactose, such as formoterol, budesonide or peptides and proteins. In this study, alternative carriers like mannitol, glucose, sorbitol, maltitol and xylitol have therefore been evaluated for their potential use in DPI formulations. Raw materials were characterised physico-chemically and blends with the model drug substance budesonide were tested with respect to the aerosolization behaviour of the powders.

It was found out that similarly to the problems known for lactose monohydrate, such as supplier variability, variability between different qualities of one supplier, the same difficulties apply to the alternative carriers investigated. Different sources and qualities of mannitol led to significant differences in the fine particle fraction (FPF), varying from 15 to 50% for two different qualities of mannitol. Similar observations were made for the other carrier materials studied. Also, the influence of conditioning the raw material at different relative humidity was found to have substantial influence on the performance of drug/carrier blends which is characterised by a strong decrease in the FPF. In summary, mannitol showed potential as a drug carrier to be used in DPIs whereas the more hygroscopic sugars only showed poor dispersibility.     

Delivery of high solubility polyols by vibrating mesh nebulizer to enhance mucociliary clearance

Abstract Background: Inhaled dry powder mannitol has established in vivo therapeutic efficacy for enhancing mucociliary function. However, a single dose necessitates multiple inhalations of a sizeable powder mass. Nebulization of mannitol by vibrating mesh devices has recently been shown in vitro to impart similar dosing in a comparable or lesser treatment time. Nevertheless, the limited solubility of mannitol restricted fluid concentrations to 150?mg/mL. The present study examines the feasibility of higher solubility polyols that presumably possess similar therapeutic properties to mannitol but deliverable at higher concentrations to shorten treatment time. A secondary aim is to compare delivery by two commercially available mesh nebulizers-the Aeroneb? Go and PARI eFlow Rapid. Methods: A series of formulations containing three polyols (mannitol, sorbitol, and xylitol) of increasing concentration in 1% w/v sodium chloride were nebulized. Aerosol characteristics and treatment times were determined primarily by laser diffraction. Results: Results indicate viscosity is the primary determinant of vibrating mesh nebulizer performance. For both nebulizers, xylitol 334?mg/mL exhibits the greatest osmolar output-double that of 150?mg/mL mannitol. Conclusions: A nebulized xylitol solution has potential clinical application for promoting rapid mucociliary clearance. Both vibrating mesh nebulizers facilitate quick treatment times. Future in vivo studies would compare the efficacy of nebulized xylitol to commercial hyperosmolar agents and establish any potential polyol-associated antibacterial activity.     

Dissolution rate enhancement of gliclazide by ordered mixing

The poorly water soluble antidiabetic drug gliclazide was selected to study the effect of excipients on dissolution rate enhancement. Ordered mixtures of micronized gliclazide with lactose, mannitol, sorbitol, maltitol and sodium chloride were prepared by manual shaking of glass vials containing the drug and excipient(s). Different water soluble excipients, addition of surfactant and superdisintegrant, drug concentration and carrier particle size influenced the dissolution rate of the drug. Dissolution rate studies of the prepared ordered mixtures revealed an increase in drug dissolution with all water soluble excipients. The order of dissolution rate improvement for gliclazide was mannitol > lactose > maltitol > sorbitol > sodium chloride. Composite granules of the particle size range 355-710 μm were superior in increasing the drug dissolution rate from ordered mixtures. Reducing the carrier particle size decreased the dissolution rate of the drug as well as the increase in drug concentration. Kinetic modeling of drug release data fitted best the Hixson-Crowell model, which indicates that all the ordered mixture formulations followed the cube root law fairly well.     

氧化苦参碱缓释微丸的制备及包衣处方因素的考察

目的:探讨制备氧化苦参碱缓释微丸的影响因素。方法:以挤出滚圆法制备含药丸芯,采用流化床包衣法,分别以HPMC E5及Eudragit RS 30D作为隔离层及控释层的包衣材料进行包衣,考察隔离层包衣增重,控释层增塑剂的种类、用量,以及包衣增重对微丸释放行为的影响。结果:优选出以2%的HPMC E5作为隔离层包衣液,并加入0.2%的PEG 400作为增塑剂,隔离层包衣增重10%;控释层包衣处方为Eudragit RS 30D 6%,滑石粉2%,增塑剂邻苯二甲酸二丁酯(DBP)2%,水90%,包衣增重10%。所制备的氧化苦参碱缓释微丸与普通微丸相比,表现出明显的缓释行为。结论:该工艺处方所制备的氧化苦参碱缓释微丸具有良好的缓释特性。     

Interaction of methylparaben preservative with selected sugars and sugar alcohols

The interaction of methylparaben preservative with selected sugars (glucose, fructose, sucrose, lactose, maltose, cellobiose) and sugar alcohols (lactitol, maltitol) were demonstrated in this study. It was observed that the formation of transesterification reaction products between methylparaben and the selected sugars occurred only under mild reaction conditions (e.g., pH 7.4 at 50 degrees C ), which were confirmed by HPLC-UV studies and mass spectrometry. On the other hand, under alkaline conditions and high temperature, degradation of the sugars predominated. Because sugars could easily undergo many possible degradation reactions and isomerization including on-column anomerization, the chromatograms of the reaction products were more complicated than those obtained from sugar alcohols. Sucrose, a nonreducing sugar, was much more stable than other selected sugars. The chromatogram of the transesterification reaction products of methylparaben with sucrose clearly showed eight peaks, which were likely to correspond to the same number of hydroxyl groups of sucrose. To compare the rate of the transesterification reaction of methylparaben with sucrose to that with sorbitol, kinetic studies were carried out. Similar rate constants were observed: 5.4 x 10(-7) L mol(-1) s(-1) and 4.9 x 10(-7) L mol(-1) s(-1) for sucrose and sorbitol, respectively.     

Raman spectroscopy for tablet coating thickness quantification and coating characterization in the presence of strong fluorescent interference

We report a novel approach to the measurement of colored tablet coating thickness, which employs Raman spectroscopy with univariate and multivariate data analysis. Our results suggest that Raman sensing can serve as a viable non-invasive means to quantify tablet coating thickness in the presence of a fluorescent ingredient in the coating formulation (food colorant Alphazurine FG or D&C Blue No. 4). This study comparatively tests the advantage of several data transformation approaches, including mean centering, standard normal variate, and Savitzky-Golay smoothed second derivative as means of improving predictive models in the presence of fluorescence. By application of the partial least squares (PLS) calibration algorithm to establish optimum covariance between transformed spectral data and measured tablet coating thicknesses, we have been able to create predictive models with calibration errors as small as 4 microm for a training set that spans colored coating thicknesses from 50 to 151 microm.     

Erosion of microbicide formulation coating layers: effects of contact and shearing with vaginal fluid or semen

An effective vaginal microbicide formulation must distribute and maintain an epithelial coating layer. The post-application durability of this coating is significantly affected by the vaginal environment. A new in vitro assay quantified coating layer erosion after contact and shear with simulated vaginal fluid or semen. Coating layer persistence and viscosity of both fluid and gel layers were assessed versus time. Five vaginal formulations were studied. In all gels, there was an overall trend of rapid ( approximately 30 min) and significant viscosity loss. Although there were differences across gels and between simulants, greater erosion occurred after contact with the low-pH vaginal fluid simulant (>50% viscosity decrease), as compared to an alkaline semen simulant. These in vitro results suggest significant differences in vivo of vaginal coating retention by the test gels. This new assay can be diversified to create a spectrum of biologically relevant conditions which collectively simulate the natural history of vaginal formulation residence.     

The effect of dietary refined sugars and sugar alcohols on renal calcium oxalate deposition in ethylene glycol-treated rats

The effect of administering refined carbohydrates in the diet on calcium oxalate deposition in the kidneys of rats given 1% (v/v) ethylene glycol in their drinking-water was investigated. The rats were given 0, 2.5, 10, 30 or 60% sucrose in the feed (w/w) and/or drinking-water (w/v) or 20% (w/w) starch, glucose, sucrose, fructose, galactose, xylitol or sorbitol in the feed for 3 wk. All of the animals remained healthy over the test period as far as could be assessed by the measurement of 19 plasma biochemical parameters. The inclusion of 30 or 60% (w/w) sucrose in the diet resulted in a more than tenfold increase in the deposition of calcium oxalate in the kidneys. However, this deposition could not be predicted from data on urinary pH and urinary excretion of calcium, oxalate and urate, which have been reported to be risk factors for stone formation. There was no evidence of increased rates of oxalate production from ethylene glycol. The administration of fructose, xylitol or sorbitol was associated with the greatest renal deposition of calcium oxalate, and glucose was associated with by far the least.     

Effect of maltodextrin and superdisintegrant in directly compressible powder mixtures prepared via co-spray drying.

The effect of maltodextrins and superdisintegrants on the tablet properties was evaluated in directly compressible powders coprocessed via spray drying. Powder mixtures containing acetaminophen, mannitol, erythritol and different maltodextrin types were prepared via co-spray drying and physically mixed with crospovidone (6% w/w, Kollidon CL) in order to evaluate the influence of maltodextrin grade (amylose/amylopectin ratio) on powder hygroscopicity, flowability, density and compactability. In addition, different superdisintegrant types and grades (6% w/w) were co-spray dried to evaluate their effect on tablet disintegration time. Tablet disintegration was affected by the amylose/amylopectin ratio of the maltodextrins. Tablets containing Glucidex 2 (1-5% amylose) had a longer disintegration time compared to Glucidex 9 (20% amylose) (11.8min versus 5.7min) and Unipure DC (50-70% amylose) (1min). The disintegration time of tablets containing a coprocessed superdisintegrant was long due to loss of superdisintegrant during processing (preferential depositing on the spray dryer wall) and was in the following order: Kollidon CL相似文献   

An assessment of powder pycnometry as a means of determining granule porosity

Abstract

Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol, mannitol, microcrystalline cellulose and calcium hydrogen phosphate dihydrate. A focus of this work was to evaluate the application of mannitol in comparison to other common fillers/binders as it was observed that this excipient is gaining more and more attention in pharmaceutical formulation development and production. While one of the main advantages of conventional fillers/binders such as lactose, microcrystalline cellulose and calcium hydrogen phosphate dihydrate is their low price level, mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the API and the patient’s body, its good compactibility and the ability to produce extremely robust tablets. Additionally, the suitability of mannitol for the emerging formulation technology of orally disintegrating tablets is pointed out. In summary, it is emphasized that the selection of the filler/binder is highly individual, depending, for example, on the preferred characteristics of the final solid dosage form, the applied API and the available budget. However, mannitol exhibits many strong advantages which can be expected to result in a more widespread application in the near future.     

盐酸伪麻黄碱脉冲小片包衣液处方优化

目的制备盐酸伪麻黄碱脉冲控释小片,并对其体外释药情况进行研究。方法制备盐酸伪麻黄碱含药片芯,采用丙烯酸树脂水分散体(Eudragit(RS 30D)制备盐酸伪麻黄碱脉冲控释小片。通过单因素实验考察药物释放的影响因素,确立处方组成,采用正交设计对包衣液处方进行优化。结果当隔离层增质量分数为2%、控释层增质量分数为5%、CMS-Na用量质量分数为25%,脉冲控释小片的时滞为6 h,体外具有脉冲释药特性。结论成功地制备了盐酸伪麻黄碱脉冲控释小片,体外释药符合脉冲释药的要求。     

Design space for a solventless photocurable pharmaceutical coating

Solventless coating technologies can overcome many of the disadvantages associated with using solvents in pharmaceutical coating. A solventless photocurable film-coating system was investigated in which liquid photocurable prepolymer and powdered pore-forming agents were applied onto non-pareil beads in a mini-coating pan. The beads were exposed to light after each coating layer. Using lactose as a filler, an optimum range of filler to photocurable polymer ratio was 1.8 to 3.0 to achieve good process efficiency and uniformity. The ratio was sensitive to particle size and filler type. The initiator concentration and light intensity also were evaluated. The time required to coat a batch was dramatically reduced compared with conventional film coating.     

Characterization,optimisation and process robustness of a co-processed mannitol for the development of orally disintegrating tablets

This is a study to fully assess a commercially available co-processed mannitol for its usefulness as an off-the-shelf excipient for developing orally disintegrating tablets (ODTs) by direct compression on a pilot scale (up to 4 kg). This work encompassed material characterization, formulation optimisation and process robustness. Overall, this co-processed mannitol possessed favourable physical attributes including low hygroscopicity and compactibility. Two design-of-experiments (DoEs) were used to screen and optimise the placebo formulation. Xylitol and crospovidone concentrations were found to have the most significant impact on disintegration time (p < 0.05). Higher xylitol concentrations retarded disintegration. Avicel PH102 promoted faster disintegration than PH101, at higher levels of xylitol. Without xylitol, higher crospovidone concentrations yielded faster disintegration and reduced tablet friability. Lubrication sensitivity studies were later conducted at two fill loads, three levels for lubricant concentration and number of blend rotations. Even at 75% fill load, the design space plot showed that 1.5% lubricant and 300 blend revolutions were sufficient to manufacture ODTs with ≤ 0.1% friability and disintegrated within 15 s. This study also describes results using a modified disintegration method based on the texture analyzer as an alternative to the USP method.