Enhanced dissolution of sildenafil citrate as dry foam tablets

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5?kg, friability test <1% with a disintegration time <5?min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.     

Pharmaceutical evaluation of ibuprofen fast-absorbed syrup containing low-molecular-weight gelatin.

Two kinds of ibuprofen syrups were prepared and evaluated. One was a suspending syrup, prepared by using hydroxypropyl methylcellulose (HPMC) as a dispersing agent, and the other was a dry syrup containing low-molecular-weight gelatin (LM gelatin). The dissolution behaviors of ibuprofen from syrups were studied, and both syrups showed size-dependent dissolution; the smaller particles exhibited faster dissolution. The in vivo absorption behaviors of the syrups were compared with that of commercial tablets of ibuprofen in beagle dogs and human volunteers. The absorption rates following oral administrations of syrups were much greater than those following administration of commercial tablets. Moreover, both syrups reduced the bitter taste and irritation of the oral mucosa caused by ibuprofen; the dry syrup markedly masked these side effects. These results suggest that the dry syrup containing LM gelatin improves some of the pharmaceutical properties of ibuprofen, and that the LM gelatin may be used in a variety of oral dosage forms.     

The Influence of Magnesium Stearate on the Hiestand Tableting Indices and Other Related Mechanical Properties of Maltodextrins

Magnesium stearate is widely used as a lubricant in pharmaceutical dosage forms. A film of magnesium stearate, or other lubricant, around individual granules is generally considered to cause the softening of tablets. Maltodextrins were chosen as model excipients since maltodextrins possessing a series of molecular weights showed systematically changing consolidation mechanisms. As maltodextrin molecular weight increases, the plasticity of the material increases. The Hiestand Tableting Indices and other related mechanical properties were used to study the effect of magnesium stearate addition on the mechanical properties and consolidation mechanisms of single component maltodextrins. Magnesium stearate was shown to lower the tensile strengths of maltodextrin compacts. Additionally, magnesium stearate addition lowered both the Hiestand Bonding Index and the Hiestand Brittle Fracture Index. The lower values of the Hiestand Brittle Fracture Index indicate that magnesium stearate promotes greater plastic behavior in maltodextrin compacts.     

The influence of magnesium stearate on the Hiestand Tableting Indices and other related mechanical properties of maltodextrins

Magnesium stearate is widely used as a lubricant in pharmaceutical dosage forms. A film of magnesium stearate, or other lubricant, around individual granules is generally considered to cause the softening of tablets. Maltodextrins were chosen as model excipients since maltodextrins possessing a series of molecular weights showed systematically changing consolidation mechanisms. As maltodextrin molecular weight increases, the plasticity of the material increases. The Hiestand Tableting Indices and other related mechanical properties were used to study the effect of magnesium stearate addition on the mechanical properties and consolidation mechanisms of single component maltodextrins. Magnesium stearate was shown to lower the tensile strengths of maltodextrin compacts. Additionally, magnesium stearate addition lowered both the Hiestand Bonding Index and the Hiestand Brittle Fracture Index. The lower values of the Hiestand Brittle Fracture Index indicate that magnesium stearate promotes greater plastic behavior in maltodextrin compacts.     

Formulation of a lyophilized dry emulsion tablet for the delivery of poorly soluble drugs

The objective was to develop a dry emulsion tablet for the flash delivery of poorly water soluble drugs using a lyophilization technique. The influence of formulation parameters on the characteristics of the lyophilized dry emulsion (LDE) tablets was investigated. Oil-in-water emulsions were made using a medium chain triglyceride as the oil phase and a maltodextrin solution (5–20% w/v) as the water phase. In addition different emulsifier-tablet binder combinations were evaluated. The emulsions were filled into PVC blisters and freeze-dried. The resulting tablets were analyzed for strength, disintegration time, porosity and residual moisture. X-ray diffractions and scanning electron micrographs (SEM) of the fracture plane of the tablets were taken. Dissolution tests were performed on lyophilized tablets containing hydrochlorothiazide (HCT) as a model drug. A significant influence of the maltodextrin type on the tablet disintegration time was seen. Maltodextrin formulations with a high dextrose equivalent (DE) value (DE38) resulted in a faster disintegration time compared to DE12 and DE24 maltodextrin formulations (p<0.05). There was a significant influence of maltodextrin concentration on tablet strength, disintegration time and porosity. Tablet strength increased significantly with increasing maltodextrin concentration (p<0.05). The porosity of the tablets made with DE38 5%, 10% and 20% (w/v) was 92%, 85% and 81%, respectively. SEM pictures showed an increase in pore diameter with a decreasing maltodextrin concentration. No significant influence of Miglyol 812 concentration on tablet strength was observed. A significant influence of methylcellulose concentration, used as emulsifier-tablet binder (Methocel^® E15LV), on tablet strength and disintegration time was observed. Dissolution tests on 25 mg HCT containing tablets resulted in a % HCT release of 35.1% and 24.1% for the LDE tablet and conventional tablet, respectively. No significant influence of the oil content in the LDE tablets on the HCT release was observed. It can be concluded that maltodextrins and methylcellulose are useful excipients in the formulation of LDE tablets. The concentration of maltodextrin, the medium chain triglyceride and methylcellulose influenced the tablet characteristics.     

Change in porosity parameters of lactose, glucose and mannitol granules caused by low compression force

The change in porosity parameters, i.e., total pore volume, porosity percentage and pore volume size distribution of lactose, glucose and mannitol granules caused by compression with a low force was investigated. In compression, fragmentation of lactose and glucose granules increased total pore volume and porosity percentage, whereas the total pore volume and porosity percentage of mannitol granules was clearly decreased. This was due to the highly porous structure of mannitol granules, which densified easily in compression. Lactose and glucose granules were shown to resist deformation more. The pore volume size distributions of lactose and glucose tablets showed that large pores ( > 14 μm) decreased in size. For mannitol tablets, the large pores vanished and simultaneously the small granule pores ( < 14 μm) reduced in size. The features of the pore structure of granules were detected in the pore volume size distributions of compressed tablets. Mercury porosimetry, assisted by scanning electron microscopy, was shown to be an adequate method to evaluate the deformation of granules in compression.     

Compression of Lactose,Glucose and Mannitol Granules

The effect of the amount of granulation liquid, compression speed and maximum compression force on the compressibility and compactibility of lactose, glucose and mannitol granules was studied. The porosity based on the geometrical shape and the uniformity of weight of tablets was also studied. Lactose and mannitol granules showed a greater compressibility than glucose granules. Mannitol granules produced the hardest tablets and lactose and glucose the weakest. The change in the amount of granulation liquid caused changes both in the granule porosity and in the amount of binder; this was attributed to differences in tablet strength. All parameters studied were relatively insensitive to changing speeds of compression in the range used, except for the breaking force of mannitol tablets, which was greatest with the lowest speed of compression. All granule masses showed a relatively good continuous flow suitable for tablet production. Tablets compressed from lactose granules had the best uniformity of weight of the tablets studied.     

Clinical trial: gluten microchallenge with wheat-based starch hydrolysates in coeliac disease patients - a randomized, double-blind, placebo-controlled study to evaluate safety

Background Wheat‐based starch hydrolysates such as glucose syrups, dextrose and maltodextrins are found in more than 50% of European processed food. These products contain low amounts of residual gluten and it has been questioned whether they are safe for coeliac disease patients. Aim To investigate whether coeliac disease patients can safely consume wheat‐based starch hydrolysate products. Methods This randomized, double‐blind, placebo‐controlled, prospective follow‐up study involved 90 coeliac disease patients in remission randomized to consume glucose syrups, maltodextrins or placebo for 24 weeks. Small bowel mucosal morphology and inflammation, symptoms, coeliac serology and malabsorption laboratory data were evaluated at baseline and at the end of the study. Results Daily ingestion of wheat‐based starch hydrolysates, glucose syrups and maltodextrins, had no deleterious effect on small‐bowel mucosal villous architecture or inflammation in coeliac disease patients when compared to the placebo group. Neither were there any significant differences in gastrointestinal symptoms, serology or malabsorption parameters after 24 weeks. Conclusions Wheat‐based starch hydrolysates, glucose syrups and maltodextrins did not have harmful effect on coeliac disease patients. Coeliac patients can thus safely continue to consume these products.     

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   

Comparison of Different Dry Binders for Roll Compaction/Dry Granulation

The suitability of different dry binders for roll compaction/ dry granulation was evaluated. Two copovidones and two crospovidones of different particle size beside three celluloses well suited for roll compaction/ dry granulation were included in the study. To classify the binders, they were compared in a binary mixture of binder and dicalciumphosphate and another formulation including a drug. Tensile strength and dissolution properties of tablets compressed from powders or granules were the focus of this study. Tablets containing the small copovidone and the small crospovidone showed the best binder properties in terms of large granule size, low fine particle fraction, and high tensile strength values. Dissolution behavior revealed a significant difference between these two binders. The dissolution of tablets containing small copovidone was significantly slower than the tablets compressed with the small crospovidone. The two copovidones showed comparable dissolution behavior, although tensile strength was higher for the type with small particles. In general, the small crospovidone was most appropriate for uncoated tablets, because it combines superior dry binding properties with fast disintegration and dissolution.     

盐酸普拉克索片剂的处方设计及质量评价

目的:通过对盐酸普拉克索片处方工艺研究的介绍,以期为国内企业研发该品种时提供有益的参考。方法:以淀粉、甘露醇为填充剂,以聚维酮K30为黏合剂,以微粉硅胶为助流剂,以硬脂酸镁为润滑剂,采用L₉(3⁴)正交设计优化各辅料的用量,以溶出度、含量均匀度为指标,进行本品的处方优化。结果:淀粉与甘露醇的用量为1:1,润湿剂为50%的乙醇溶液,黏合剂为10%的聚维酮K30,助流剂为1%的微粉硅胶,润滑剂为1%的硬脂酸镁,制备的片剂含量均匀度最佳,溶出度最接近原研处方。结论:制备的盐酸普拉克索片剂外观光洁,含量均匀度好,药物溶出行为达到了预期的目的。     

Comparison of different dry binders for roll compaction/dry granulation

The suitability of different dry binders for roll compaction/ dry granulation was evaluated. Two copovidones and two crospovidones of different particle size beside three celluloses well suited for roll compaction/ dry granulation were included in the study. To classify the binders, they were compared in a binary mixture of binder and dicalciumphosphate and another formulation including a drug. Tensile strength and dissolution properties of tablets compressed from powders or granules were the focus of this study. Tablets containing the small copovidone and the small crospovidone showed the best binder properties in terms of large granule size, low fine particle fraction, and high tensile strength values. Dissolution behavior revealed a significant difference between these two binders. The dissolution of tablets containing small copovidone was significantly slower than the tablets compressed with the small crospovidone. The two copovidones showed comparable dissolution behavior, although tensile strength was higher for the type with small particles. In general, the small crospovidone was most appropriate for uncoated tablets, because it combines superior dry binding properties with fast disintegration and dissolution.     

Direct compression and moulding properties of co-extruded isomalt/drug mixtures

Isomalt, a disaccharide alcohol was co-extruded with paracetamol or hydrochlorothiazide (HCT) in order to improve its tabletting properties. After extrusion, isomalt was transformed into an amorphous form, while paracetamol remained crystalline. Hot stage microscopy showed that HCT was amorphous in the isomalt carrier up to a concentration of 1% (w/w). Direct compression of mixtures formulated with co-extruded isomalt/paracetamol powders yielded harder tablets compared with physical mixtures and no powder agglomeration was observed. Direct moulding of isomalt co-extruded with either paracetamol or HCT was feasible, yielding hard tablets. A fast dissolution rate was seen for both the compressed and the moulded tablets (>80% paracetamol and 60% HCT released within 20 min). The compressed tablets showed a dramatic decrease in tensile strength during storage at 85% RH, while the tensile strength of the moulded tablets remained above 0.80 MPa after 6 months storage at the same conditions. Co-extrusion of isomalt with paracetamol and HCT dramatically improved the tabletting properties of the mixtures (compared with physical mixtures of drug and isomalt). Direct moulding proved to be a suitable technique to produce isomalt based tablets.     

The effect of incorporation technics of water soluble macromolecular binders on the properties of fluidized-bed dried granules

Five binders characterized by particle size and dissolution rate have been studied in order to evaluate their qualification for fluidized-bed granulation. For this purpose they were applied as powder and solution, respectively. Quality parameters of the granules and tablets obtained were compared. Compared with solutions of binders the dry incorporation of the binder led to a slower growth of the granules mainly depending on the dissolution rate of the binders. Due to this fact the formulations showed a decreased strength except PVP (high dissolution rate) which causes an increased growth of the granules at the same time. A size reduction of binders with a low dissolution rate led to tablets with characteristics of strength similar to the findings when solutions of binders were used, whereas the growth of granules remained uninfluenced.     

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.     

Wax beads as cushioning agents during the compression of coated diltiazem pellets.

Placebo particles were mixed with film-coated diltiazem pellets to evaluate them as cushioning agents during tabletting in order to protect the film coat from damage. The cushioning properties of alpha-lactose monohydrate granules, microcrystalline cellulose pellets and wax/starch beads were evaluated by comparing the dissolution profile of the coated pellets before and after compression (compression force 10 kN). Only the tablet formulations containing wax/starch beads provided protection to the film coat. However, the dissolution rate of tablets formulated with waxy maltodextrin/paraffinic wax placebo beads was too slow as the tablets did not disintegrate. Adding 50% (w/w) drum-dried corn starch/Explotab/paraffinic wax beads to the formulation was the optimal amount of cushioning beads to provide sufficient protection for the film coat and yield disintegrating tablets. Using a compression simulator, the effect of precompression force and compression time on the dissolution rate was found to be insignificant. The diametral crushing strength of tablets containing 50% (w/w) drum-dried corn starch/Explotab/paraffinic wax beads was about 25.0 N (+/-0.3 N), with a friability of 0.4% (+/-0.04%). This study demonstrates that adding deformable wax pellets minimizes the damage to film-coated pellets during compression.     

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.     

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets.

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.     

Enhancement of ibuprofen dissolution via wet granulation with beta-cyclodextrin

The purpose was to investigate the effect of wet granulation with beta-cyclodextrin (betaCD) on the enhancement of ibuprofen (IBU) dissolution. The effect of the granulation variables on the physical properties as well as the dissolution of tablets prepared from these granules was also examined. Granulation was performed using three granulating solvents: water, ethanol (95 vol%), and isopropanol. Granules were either oven-dried for 2 h or air-dried for 3 days. The granules or respective physical mixtures were compressed into tablets. Powder X-ray diffraction showed that oven-dried granulation resulted in less amorphous entities thatfacilitated IBU-betaCD complexation in solution and enhanced the dissolution of the corresponding tablets compared to the physical mixture with or without oven drying. In contrast, air-dried granulation did not cause any differences in the X-ray diffraction pattern (crystallinity) or the dissolution compared to the physical mixture without drying. Isopropanol and water, as granulating solvents, enhanced the dissolution of the oven-dried batches more than ethanol. The Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA) data showed that tablets prepared from oven-dried granules, but not air-dried granules, had lower AH values and percent loss in weight, respectively, than those prepared from the physical mixture as a result of the expulsion of the water molecules from the betaCD cavity and enhancement of the complexation in solution. These results showed that oven-dried granulation of IBU and betaCD provided faster IBU dissolution than the physical mixture; air-dried granulation did not substantially affect the dissolution of IBU.     

Effect of Hydrophilic Diluents on the Release Profile of Griseofulvin from Tablet Formulations

Studies have shown that when compressing drugs with low aqueous solubility, the solubility of diluents selected is very crucial as it influences the disintegration, dissolution and bioavailability of such drugs. Based on these reports, the present study was undertaken to investigate the effect of some commonly used hydrophilic tablet diluents (lactose, sucrose, mannitol and dextrose) on the in vitro release properties of griseofulvin from compressed tablets. Griseofulvin granules and tablets were prepared using the wet granulation method. Tablet properties evaluated as a function of the diluents used include, hardness, friability, dissolution profile and dissolution efficiency at 60 min. Results obtained indicated variability in griseofulvin release in the presence of the diluents. The relative enhanced dissolution effects of the four hydrophilic diluents is in the order of dextrose>sucrose>lactose>mannitol. All the griseofulvin tablet batches produced exhibited a better drug release (in terms of rate and extent of release) than a commercially available tablet sample of griseofulvin (Fulcin^®). The results of the dissolution efficiency (DE_60min) are 91.7, 83.5, 48.7, 35.3 and 15.6% for dextrose, sucrose, lactose, mannitol and fulcin^®, respectively. The overall results indicated that dextrose or sucrose can be utilised to improve the in vitro release profile and hence in vivo bioavailability of griseofulvin from compressed tablets.