Resistant starch as a carrier for oral colon-targeting drug matrix system

In this study, a novel tablet of protein drug matrix for colon targeting was developed using resistant starch as a carrier prepared by pre-gelatinization and cross-linking of starch. The effects of pre-gelatinization and cross-linking on the swelling and enzymatic degradation of maize starch as well as the release rate of drug from the matrix tablets were examined. Cross-linked pre-gelatinized maize starches were prepared by double modification of pre-gelatinization and cross-linked with POCl₃, and bovine serum albumin was used as a model drug. For in vitro drug release assays, the resistant starch matrix tablets were incubated in simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid, respectively. The content of resistant starch and swelling property of maize starch were increased by pre-gelatinization and cross-linking, which retarded its enzymatic degradation. Drug release studies have shown that the matrix tablets of cross-linked pre-gelatinized maize starch could delivery the drug to the colon. These results indicate that the resistant starch carrier prepared by pre-gelatinization and cross-linking can be used for a potential drug delivery carrier for colon-targeting drug matrix delivery system.     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.     

Zero-order release of theophylline from a core-in-cup tablet in sequenced simulated gastric and intestinal fluid

Core-in-cup tablets containing theophylline were evaluated for their dissolution characteristics in sequenced simulated gastric fluid (SGF) followed by simulated intestinalfluid (SIF). Core-in-cup tablets containing 10% w/w, 20% w/w, and 30% w/w acacia as binder were evaluated for their effects on the time course of release of theophylline. This was done to optimize a formula that could release theophylline at a zero-order rate of release for 8-16 hr in simulated gastrointestinal fluids. Theophylline was released and dissolved from the core-in-cup tablets at a rate that is more consistent with a zero-order dissolution rate than a first-order dissolution rate in both SIG and SIF. The dissolution rates of theophylline from the 10%, 20%, and 30% acacia core-in-cup tablets were 0.87 mg/min, 0.53 mg/min, and 0.27 mg/min, respectively in SGF, and 0.61 mg/min, 0.30 mg/min, and 0.20 mg/min, respectively in SIF. The results indicate that a concentration of 32% w/w acacia in the core tablet will release theophylline at a rate of 0.14 mg/min in SGF for 2 hr followed by SIF for 10 hr.     

The Effect of Compaction Force and Type of Pregelatinized Starch on the Dissolution of Acetaminophen

Abstract

The influence of four pregelatinized starches—National® 1551, Lycatabps, Pregeflo®M, and Starch 1500®—as binders, on the dissolution of acetaminophen was evaluated in a model wet-granulated system. Systems containing 82% acetaminophen were prepared under the same processing conditions and compacted to three target tablet thicknesses. The dissolution performance was assessed using a point estimate of percent dissolved at 30 min (%T₃₀) as well as dissolution eflciency through 30 min (DE₃₀). All four binders evaluated meet USP requirements for purity. National 1551, Lycatab PGS, and Starch 1500 were not affected by compaction force in terms of dissolution performance. Differences were observed between the fully pregelatinized systems of National 1551 and Lycatab PGS, in comparison to the partially pregelatinized system, Starch 1500. The Pregeflo M starch produced a system with delayed drug dissolution and was influenced by compaction force.     

酶响应型捏合淀粉药物载体的制备和性能

采用机械捏合的方法制备了不同抗消化性能的捏合淀粉基载体材料。利用扫描电子显微技术(SEM)、X射线衍射技术(XRD)和体外模拟人体消化试验(In-Vitro)对捏合淀粉的颗粒形貌、结晶结构和在人体上消化道中的消化性能进行了考察。发现随着抗消化性能的降低,淀粉颗粒的破损程度越大,淀粉结晶结构结晶形态由B型向V型转变,消化速度增大。同时以胰酶为模型药物,考察了捏合淀粉对药物的体外释放性能。结果显示,不同抗消化性能的捏合淀粉可望作为不同消化道靶向要求的药物载体材料。     

Release of diltiazem hydrochloride from hydrophilic matrices of polyethylene oxide and carbopol

The mucoadhesion, swelling, and drug release behavior of polyethylene oxide (PEO) and carbopol (CP) matrices were studied using a water soluble model drug diltiazem hydrochloride. The mucoadhesive strength of the matrices increased with increase in polymer content. The results showed that PEO was more mucoadhesive than CP. Mucoadhesion of the tablets was dependent upon the swelling. Swelling was ascertained by measuring the axial and radial expansion of matrix tablets following exposure to media of physiological ionic strength. There was a marked increase in the swelling index of matrices containing high polymer content of PEO as compared to CP. Drug release kinetics were found to be closely related to dissolution and swelling properties of the matrices. The release was found to be non-fickian with n (release exponent) values ranging from 0.45-0.58. At a constant polymer content (15.84% w/w), the main contributing factor for the mucoadhesion, swelling, and release was the amount of PEO.     

Effect of Viscosity Increasing Agent and Electrolyte Concentration on the Release Rate of Theophylline from a HPMC Based Sustained Release Capsules

Abstract

Sustained release (SR) granules (250-650～) containing theophylline were prepared using hydroxypropyl methylcellulose (HPMC) as a rate retarding polymer. The effect of variable ionic strength and viscosity increasing agent on the theophylline release rate have been investigated. Irrespective of dissolution media the theophylline release kinetics was found to be dependent on square root of time. Thc Higuchian release rate (K) was found to increase exponentially with the increase in ionic strength of the dissolution fluid. An opposite effect was observed with the viscosity increasing agent sodium carboxy methyl cellulose (Na-CMC) in the dissolution fluid. The release rate dccreased linearly with the increase of Na-CMC concentration in the dissolution fluid.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

Chitin and Chitosan as Disintegrants in Paracetamol Tablets

Chitin and chitosan as disintegrants in paracetamol tablets were evaluated and compared to four commonly used disintegrants. Tablets containing chitosan showed faster disintegration, greater dissolution and was slightly softer than those containing chitin. An increment in concentration of these polymers caused markedly faster disintegration and better dissolution while an increase in compressional force showed opposite effects. Aging slightly altered the disintegration and dissolution. Tablets containing 7% of chitosan disintegrated within one minute which was much faster than those containing corn starch and microcrystalline cellulose but slightly slower than those containing sodium starch glycolate and croscamellose sodium. However, their dissolution profiles were non-significantly different from those of the latter ones.

Crystallinity, degree of acetylation, chain length and particle size were attributed to the efficiency of chitin and chitosan. Moisture sorption and water uptake were found to be the major mechanisms of disintegration while dissolution related to the swelling capacity.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

Abstract

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

Chitin and Chitosan as Disintegrants in Paracetamol Tablets

Abstract

Chitin and chitosan as disintegrants in paracetamol tablets were evaluated and compared to four commonly used disintegrants. Tablets containing chitosan showed faster disintegration, greater dissolution and was slightly softer than those containing chitin. An increment in concentration of these polymers caused markedly faster disintegration and better dissolution while an increase in compressional force showed opposite effects. Aging slightly altered the disintegration and dissolution. Tablets containing 7% of chitosan disintegrated within one minute which was much faster than those containing corn starch and microcrystalline cellulose but slightly slower than those containing sodium starch glycolate and croscamellose sodium. However, their dissolution profiles were non-significantly different from those of the latter ones.

Crystallinity, degree of acetylation, chain length and particle size were attributed to the efficiency of chitin and chitosan. Moisture sorption and water uptake were found to be the major mechanisms of disintegration while dissolution related to the swelling capacity.     

Evaluation of the emulsifying properties of some cationic starches

Different cationic potato, maize, and waxy maize starches were evaluated for their emulsifying properties. Emulsions were prepared using 20% (w/w) arachidic oil and 80% (w/w) water. Emulsions with the cationic starches as emulsifier in a concentration ranging from 1% to 5% (w/w) were prepared and characterized by droplet size and viscosity measurements, and the stability was evaluated visually and by electrical conductance measurements. None of the cationic potato, waxy maize starches, and maize starches with a low degree of substitution (DS) showed adequate emulsifying properties. Emulsions prepared using non-pregelatinized (C ☆ bond 05914, 2% and 5% w/w; C ☆ bond 05907, 5% w/w) and pregelatinized (C ☆ bond 12504, 5% w/w) cationic maize starches with high-DS were visually stable. The initial mean droplet volume diameter of the emulsions prepared with these cationic starches in a 5% (w/w) concentration was similar and ranged from 2.40 to 2.84 μm however, there was an important difference in droplet size distribution. The droplet size distribution of the emulsions prepared using the non-pregelatinized high-DS cationic starches was markedly narrower than in the case of the emulsions prepared using the pregelatinized high-DS cationic starches. The droplet size of the emulsions remained almost constant during 120 days of storage. Visual inspection and electrical conductance measurements showed that these emulsions were stable for at least 120 days.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

Compressional characteristics of native and pregelatinized forms of sorghum,plantain, and corn starches and the mechanical properties of their tablets

A study was made of the compressional characteristics of native and pregelatinized forms of sorghum, plantain, and corn starches and the mechanical properties of their tablets. Compressional characteristics were analyzed using density measurements and the Heckel and Kawakita plots. Pregelatinized starches exhibited more densification than native starches during die filling and at low pressures. The ranking for the mean yield pressure (Py) values for the starches was plantain < corn < sorghum, with the pregelatinized starches having lower values than the native starches. The ranking for the values of another pressure term, Pk--an inverse measure of plasticity, was corn < plantain < sorghum, but with the native starches having the lower values. For the tablets, the ranking for values of tensile strength (T) was corn > plantain > sorghum, while the ranking for the brittle fracture index (BFI) was plantain > corn > sorghum. Tablets made from pregelatinized starches had lower T and BFI values than those made from native starches. The results suggest that pregelatinization of the starches facilitated faster onset of plastic deformation but reduced the amount of plastic deformation which occurred during the compression process.     

Effect of anionic water-soluble dyes on film coating properties of chitosan acetate

Solution of chitosan in dilute acetic acid was prepared to have an apparent viscosity of 125 mPa s and mixed with solution of anionic water-soluble dye. The effects of concentration and type of dye and molecular weight and percentage deacetylation of chitosan on their miscibility and physical stability were investigated. High concentration of dye and high molecular weight and percentage deacetylation of chitosan resulted in precipitation or colloidal dispersion due to ionic interaction between dye and the polymer. The effect was more prominent upon storage. The miscibility of dye and the polymer depended on the molecular configuration and ionic group in the dye molecule. It was ranked brilliant blue approximately euqal to green FS > fast green > ponceau SX approximately euqal to green sunset yellow > erythrosine approximately euqal to green tartrazin > indigo carmine. Solutions of low molecular weight chitosan with and without green FS were then used as coating formulations onto propranolol hydrochloride core tablets. There was no color migration on coated tablets even after storage for 1 year. Disintegration and drug dissolution from tablets coated with colored film were slightly slower than those from tablets coated with plain film and core tablet, respectively. This was corresponding to the results of swelling and dissolution of cast films. However, all tablets conformed to the specification in monograph of USP XXIV.     

The Effect of Some Surfactants on the in- Vitro Properties of Double Compressed Tablets

The effect of different types and concentrations of some surface active agents as well as the method of surfactant incorporation on the in - vitro properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U. S. P. official tests and some other selected non-official tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Incorporation of a low concentration (0.2 % w/w) of surface active agents i n the formulation of tablets decreased the disintegration time but did not affect their dissolution rate. Higher concentrations of surface active agents retarded the dissolutiono of tablets. Non ionic surfactants showed higher regarding effect than ionic surfactants . Changing the method of surfactant incorporation did not greatly affect the dissolution rate of tablets.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Abstract

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

微波辐射对高链玉米淀粉热性质的影响

采用微波对30%水分含量的高链玉米淀粉进行处理。结果表明,微波处理降低了淀粉的膨胀度和溶解度、冻溶稳定性以及焓值,提高了糊化转变温度及转变温度范围。高链玉米淀粉经处理后糊化起始温度升高、黏度降低,黏度曲线由C型变为D型。以上表明在淀粉颗粒内无定型区和结晶区的直链淀粉与直链淀粉、直链淀粉与支链淀粉发生交互作用,产生了新的不同稳定性的结晶体,从而导致微波淀粉内部更加有序的结晶排列。     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

Abstract

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile than was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile than was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.