Evaluation of the effect of carrier material on modification of release characteristics of poor water soluble drug from liquisolid compacts.

Liquisolid compact is a novel dosage form in which a liquid medication (liquid drug, drug solution/dispersion in non-volatile solvent/solvent system) is converted to a dry, free flowing powder and compressed. Objective of the study was to elucidate the effect of carrier material on release characteristics of clopidogrel from liquisolid compacts. Different formulations of liquisolid compacts were developed using microcrystalline cellulose, starch maize, polyvinyl pyrollidone and hydroxypropyl methylcellulose as carrier material in three concentrations (40, 30 and 20%, w/w). Liquid vehicle was selected on the basis of solubility of clopidogrel. Colloidal silicondioxide was used as coating material and ratio of carrier to coating material was kept 10. A control formulation comprised of microcrystalline cellulose (diluents), tabletose-80 (diluents), primojel (disintegrant) and magnesium stearate (lubricant) was prepared by direct compression technique and was used for comparison. All the formulations were evaluated at pre and post compression level. Acid solubility profile showed higher solubility in HCl buffer pH2 (296.89±3.49 µg/mL). Mixture of propylene glycol and water (2:1, v/v) was selected as liquid vehicle. Drug content was in the range of 99-101% of the claimed quantity. All the formulations showed better mechanical strength and their friability was within the official limits (<1%). Microcrystalline cellulose and starch maize resulted in faster drug release while polyvinyl pyrollidone and HPMC resulted in sustaining drug release by gel formation. It is concluded from results that both fast release and sustained release of clopidogrel can be achieved by proper selection of carrier material.

Molecular-structure evolution during in vitro fermentation of granular high-amylose wheat starch is different to in vitro digestion.

This study investigates the evolution of the distributions of whole molecular size and of chain length of granular wheat starches (37 ~ 93% amylose content), subjected to in vitro fermentation with a porcine faecal inoculum or digestion with pancreatic enzymes. The results showed that the molecular structures of high-amylose starch (HAS) unfermented residues largely remained unchanged during the fermentation process, while wild-type starch (37% amylose content) showed a preferential degradation of the amylopectin fraction. In contrast, under simulated digestion conditions, the undigested residues of HAS showed structural changes, including a decrease in amylose content, a shift of amylose peak position towards lower degrees of polymerisation, and an enzyme-resistant fraction. These changes of starch structure are likely to be dependent on the different starch-degrading enzyme activities present in pancreatic vs. microbial systems. Molecular changes in response to fermentation metabolism revealed by size-exclusion chromatography can help understand the microbial utilization of resistant starch.

Effect of four viscous soluble dietary fibers on the physicochemical, structural properties, and in vitro digestibility of rice starch: A comparison study.

The effect of carboxymethyl cellulose (CMC), high-methoxyl pectin (HMP), konjac glucomannan (KGM), and xanthan gum (XG) on the physicochemical, structural properties, and digestibility of rice starch were investigated and compared. The four viscous soluble dietary fibers (VSDFs) increased the viscosity, storage modulus and loss modulus while decreased the pasting temperature and gelatinization enthalpy. Moreover, XG produced the lowest peak viscosity and dynamic modulus compared with the other VSDFs. Furthermore, the degree of short-range ordered structure of starch with KGM increased from 0.8448 to 0.8716; and the relative crystallinity of starch with XG increased by 12%. An ordered and reunited network structure was observed in SEM. In addition, VSDF inhibited the digestibility of rice starch and significantly increased the resistant starch content. This study compared the effect of four VSDFs on the physicochemical, structural and digestion properties of rice starch to fully understand and develop their application to starchy foods.

Investigation of starch functionality and digestibility in white wheat bread produced from a recipe containing added maltogenic amylase or amylomaltase.

In the crumb of fresh white wheat bread, starch is fully gelatinized. Its molecular and three-dimensional structure are major factors limiting the rate of its digestion. The aim of this study was to in situ modify starch during bread making with starch-modifying enzymes (maltogenic amylase and amylomaltase) and to investigate the impact thereof on bread characteristics, starch retrogradation and digestibility. Maltogenic amylase treatment increased the relative content of short amylopectin chains (degree of polymerization ≤ 8). This resulted in lower starch retrogradation and crumb firmness upon storage, and reduced extent (up to 18%) of in vitro starch digestion for fresh and stored breads. Amylomaltase only modestly shortened amylose chains and had no measurable impact on amylopectin structure. Modification with this enzyme led to slower bread crumb firming but did not influence starch digestibility.

Insights into the multi-scale structural properties and digestibility of lotus seed starch-chlorogenic acid complexes prepared by microwave irradiation.

By inspecting starch hierarchical structural evolution, this work explored how microwave irradiation tailored the digestion characteristics of lotus seed starch-chlorogenic acid mixtures. The results showed that after microwave treatment, the granular structure, short-range ordered structure, helical conformation, and lamellar structure of starch exhibited different degrees of disorganization. In this procedure, chlorogenic acid interacted with starch molecules to form lotus seed starch-chlorogenic acid complexes and participated in the reorganization of the matrixes of the starch substrate in three forms: V-type inclusion complex, non-inclusion complex, and simply physically entrapped. These structural changes, coupled with the inhibition of chlorogenic acid on carbohydrate hydrolyzing enzymes, contributed to the slowly digestible features of lotus seed starch-chlorogenic acid complexes. This study provided a basis for understanding the multi-scale structure-digestibility relationship of starchy foods rich in phenolic acids under microwave treatment.

Structural changes of A-, B- and C-type starches of corn, potato and pea as influenced by sonication temperature and their relationships with digestibility.

The effect of sonication temperature on the structures and digestion behaviour of corn starch (CS, A-type), potato starch (PtS, B-type), and pea starch (PS, C-type) was investigated. For CS, sonication temperature resulted in a rough surface, decreased apparent amylose content, gelatinization enthalpy and gelatinization degree, increased short-range orders, long-range orders, retrogradation degree and resistant starch content. For PtS, sonication temperature led to a coarser surface with scratches, increased apparent amylose content and gelatinization degree, decreased short-range orders, long-range orders, gelatinization enthalpy, retrogradation degree, and resistant starch content. For PS, sonication temperature showed partial disintegration on surface, increased gelatinization degree, decreased apparent amylose content, short-range orders, long-range orders, gelatinization enthalpy, retrogradation degree and resistant starch content. This study suggested that starch digestion features could be controlled by the crystalline pattern of starch used and the extent of sonication temperature, and thus were of value for rational control of starch digestion features.

Starch-lipid interaction alters the molecular structure and ultimate starch bioavailability: A comprehensive review.

Starch bioavailability which results in eliciting postprandial glycaemic response, is a trait of great significance and is majorly influenced by the physical interaction among the matrix components governed by their molecular structure as well as dynamics. Among physical interactions limiting starch bioavailability, starch and any guest molecules like lipid interact together to alter the molecular structure into a compact V-type arrangement endorsing the processed crystallinity, thus limiting carbolytic enzymatic digestion and further bioavailability. Considering the importance of starch-lipid dynamics affecting bioavailability, intensive research based on endogenous (internal lipids which are embedded into the food matrix) as well as exogenous (those are added from outside into the food matrix during processing like cooking) lipids have been carried out, endorsing physical interactions at colloidal and microstructural levels. The shared insights on such binary (starch-lipid) interactions revealed the evolution of characterization techniques as well as their role on altering the functional and nutritional value. It is very much vital to have a thorough understanding about the mechanisms on the molecular level to make use of these matrix interactions in the most efficient way, while certain basic questions are still remaining unaddressed. Do starch - lipid complexation affects the ultimate starch bioavailability? If so, then whether such complexation ability depends on amylose - fatty acid/lipid content? Whether the complexation is influenced further by fatty acid type/concentration/chain length or saturation? Further comprehending this, whether the altered bioavailability by binary (starch-lipid) could further be affected by ternary (starch-lipid-protein) and quaternary (starch-lipid-protein-phenolics) interactions are also discussed in this comprehensive review.

In vitro digestion rate of fully gelatinized rice starches is driven by molecular size and amylopectin medium-long chains.

In current study, the effects of starch fine molecular structures on its in vitro digestibility at fully gelatinized stage were investigated. The digestion kinetics of 15 fully gelatinized rice starches were obtained and correlated with starch chain-length distributions and molecular size distributions. Both logarithm of slopes and parallel first-order kinetic model were applied to fit the digestion curves to a few kinetics-based parameters. Result showed there were two simultaneous digestion fractions (fast versus slow) for fully gelatinized rice starches. The rate constants of slowly-digestible fraction significantly correlated with starch molecular sizes, especially with that of amylopectin molecules. Hydrodynamically larger amylopectin molecules tend to contain more shorter branches but less long chains. This slows down the starch hydrolysis by α-amylase while the action of AMG is less antagonistically hindered, increasing overall digestion rate. This study provides important information for rice breeders and manufacturers to develop rice products with reduced starch digestibility.

Functionality and starch digestibility of wrinkled and round pea flours of two different particle sizes.

Wrinkled and round peas (two varieties each type) cultivated in two locations were milled to obtain fine and coarse wrinkled (WPF) and round pea flour (RPF). WPF exhibited markedly increased pasting viscosities at 120 and 140 °C compared with 95 °C. Overall, the pasting properties of WPF were considerably lower than those of RPF. Resistant starch (RS) contents of cooked WPF (17.2-22.2%, dsb) were significantly larger than those of RPF (7.9-11.4%), resulting from higher starch gelatinization temperatures, greater amylose contents, and presence of more protein and fiber in WPF. The two particle sizes affected the water-holding capacity (WHC) of WPF, gelatinization enthalpy changes (ΔH) of WPF and RPF, and pasting properties and starch digestibility of RPF. Pearson correlation and principal component analysis (PCA) were conducted to reveal the relationships among the techno-functional parameters of pea flours. Wrinkled pea showed promise to generate new pea flours with distinct functionality and enhanced nutritional value.

Rice and common bean blends: Effect of cooking on in vitro starch digestibility and phenolics profile.

This study aims to evaluate the effects of in vitro digestion of rice and common bean blends on phenolics content and profile. Black and carioca beans were used as common bean sources. Blends consisted of 25:75, 50:50, and 75:25 polished rice:beans (w/w). Pure rice or pure beans were also analyzed. Phenolic compounds were determined in raw, cooked, and digested samples. The glucose release through in vitro digestion was slower as the proportion of black beans or carioca beans increased. Starch digestibility ranged between 41.1 in 100% carioca bean to 84.4% in 100% rice. Hydroxybenzoic acid, ferulic acid, p-coumaric acid, catechin, and epicatechin were the most abundant phenolics detected in the studied samples. Considering the content of phenolic compounds determined in the raw, cooked, and digested grains, only a small fraction was available for absorption in the gut, with amounts varying from 0.1 to 0.6 µg·g-1.

Inhibition of starch digestion: The role of hydrophobic domain of both α-amylase and substrates.

The physicochemical mechanism of starch digestion is very complicated since it may be affected by the non-valence interactions of the amylase inhibitor with the substrate or the enzyme. The role of hydrophobic interaction in the process of starch digestion is not clear. In this study, pluronics (PLs) with different hydrophobicity were used as model amphiphilic compounds to study their inhibition on starch digestion using multi-spectroscopic methods. The results showed that the hydrophobic nature of PLs changed starch structure, but it had a greater effect on the structure of α-amylase by exposing more tryptophan residues and increasing α-helix and ß-sheet contents. Further investigation by using different chain-length fatty acids confirmed the results. The finding in this study is informative to design and fabricate α-amylase inhibitors for controlling starch digestion at the molecular level.

Effects of soluble dietary fibers on the viscosity property and digestion kinetics of corn starch digesta.

Four soluble dietary fibers (SDFs) were fortified with corn starch (CS) at different concentrations to match the same viscosity equivalents. The mixtures were subjected to a simulated digestion procedure to study the effects of SDFs on viscosity properties and digestion kinetics of CS. Results showed that SDFs increased the hydration property and decreased the water mobility of digesta. During digestion process, SDFs increased the apparent viscosity of digesta to some extent, and showed significant difference to delay the decay of digesta viscosity (kv). The amylolysis inhibitory ability was similar when each SDF was present at the same viscosity equivalent, however, significant differences were found on the digestion rate constant of k2. Linear correlations between kv and k2 were established for 1 and 2 equivalent groups. These results demonstrated that SDFs could delay the digestion process as chemistry differences, which related to their ability on delaying the change of digesta viscosity.

Proanthocyanidins from Chinese berry leaves modified the physicochemical properties and digestive characteristic of rice starch.

Proanthocyanidins extracted from Chinese berry leaves (CBLPs) were heated with rice starch in aqueous solution to prepare polyphenols-starch complexes. The physicochemical properties of the complexes were characterized with XRD, DSC, RVA and FT-IR and starch constituents were also analyzed with an enzyme method. Results indicated that the addition of CBLPs destroyed the long ordered structure of rice starch rather than the short ordered structure, since the crystallinity decreased from 21.96% to 18.90% and the ratio of 1047 cm-1/1022 cm-1 showed little difference, consistent with the lower ΔH of complexes with higher CBLPs content. Additionally, the CBLPs-rice starch complexes showed a significantly lower content of rapidly digested starch (RDS, 45.64 ± 3.25%) than that of the native rice starch (67.76 ± 2.15%). These results indicated that CBLPs complexes with rice starch might be a novel way to prepare functional starch with slower digestion.

Design and Validation of a Diet Rich in Slowly Digestible Starch for Type 2 Diabetic Patients for Significant Improvement in Glycemic Profile.

This study aimed at designing a-diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and classified as being either high (high-SDS) or low (low-SDS) in SDS (in vitro SDS method). A randomized controlled cross-over pilot study was performed: Eight patients with T2D consumed randomly a high-SDS or a low-SDS diet for one week each, while their glycemic profile was monitored for 6 days. Based on 250 food product SDS analyses and dietary recommendations for patients with T2D, the high-SDS and low-SDS diets were designed. The high-SDS diet significantly increased SDS intake and the SDS/carbohydrates proportion compared to the low-SDS diet (61.6 vs. 11.6 g/day and 30% vs. 6%; p < 0.0001, respectively). Increasing the SDS/carbohydrate proportion to 50% of the meal was significantly correlated with a 12% decrease in tAUC0-120 min and a 14% decrease in the glycemic peak value (p < 0.001 for both). A high-SDS diet can be easily designed by carefully selecting commercial starchy products and providing relevant recommendations for T2D to improve their glycemic profile.

Removal of starch granule-associated proteins promotes α-amylase hydrolysis of rice starch granule.

Starch granule-surface proteins (SGSPs) and granule-channel proteins (SGCPs) are granule-associated proteins (SGAPs), which have been found to be distributed on the surface and channels of starch granules, respectively. To investigate the impacts of SGAPs on α-amylase hydrolysis of starch, SGCPs or SGAPs of waxy, low and high amylose rice starches were removed. Removal of SGAPs or SGCPs greatly increased hydrolysis rate of rice starches. Meanwhile, these granules incurred a greater number and size of pores on their surfaces during hydrolysis. Compared to low and high amylose starches, waxy starch before and after removing SGAPs exhibited a higher hydrolysis rate. Rice starch hydrolysis began with enlargement of cavity and channels both horizontally and vertically. XRD analysis revealed that removal of SGAPs decreased relative crystallinity (RC) of starch and advanced changes in RC during hydrolysis process. This study provides new information about the role of SGAPs in the mechanisms of α-amylase hydrolysis.

Intact endosperm cells in buckwheat flour limit starch gelatinization and digestibility in vitro.

The objective of this study was to determine the biophysical properties of buckwheat (BW) endosperm and their influences on detachment of intact cells, starch gelatinization and digestibility. The intact cells were isolated from BW kernels by dry milling and sieving. The microscopy and texture analysis showed intact endosperm cells could be detached easily due to the fragile structure and low hardness of BW endosperm. More than 70% intact cells were found in commercial light flour. The starch granules entrapped in intact cells exhibited a delay gelatinization and restricted swelling behavior (2-3 â„ƒ higher onset gelatinization temperature than isolated starch). Starch in BW flour had a markedly lower extent of digestion compared to the broken cells and isolated starch. This study provided a new mechanistic understanding of low glycemic index of BW food, and could guide the processing of BW flour to retain slow digestion properties.

Inhibitory effect of chestnut (Castanea mollissima Blume) inner skin extract on the activity of α-amylase, α-glucosidase, dipeptidyl peptidase IV and in vitro digestibility of starches.

This study aimed to investigate the inhibitory effect of chestnut inner skin extract (CISE) on the activity of postprandial blood sugar-related enzymes. In total, 12 flavonoids were identified by HPLC-TOF-MS. CISE showed strong and weak inhibition on α-amylase and α-glucosidase, with the IC50 of 27.2 and 2.3 µg/mL, respectively. The inhibition modes of CISE against α-amylase and α-glucosidase were mixed-type and non-competitive type, respectively. Epicatechin gallate noncompetitively inhibited α-amylase, α-glucosidase and dipeptidyl peptidase IV (DPP-IV). Analysis by ultraviolet-visible spectroscopy, fluorescence spectroscopy and circular dichroism suggested that flavonoids altered the hydrophobicity and microenvironment of these enzymes. CISE decreased the starch bioavailability by reducing the enzymatic hydrolysis rate and increasing the fraction of undigested starch. The extract reduced the rapidly digestible starch and increased the resistant starch after incorporation into A-, B- or C- crystallinity starch. Thus, the chestnut inner skin is a useful resource for regulating postprandial blood sugar level.

Cake of brown, black and red rice: Influence of transglutaminase on technological properties, in vitro starch digestibility and phenolic compounds.

This study aimed to evaluate the influence of transglutaminase addition on the technological properties and in vitro starch digestibility of gluten-free cakes of brown, black, and red rice, as well as the effect of baking on the content of phenolic compounds. Transglutaminase addition exerted significant effect in the technological properties only in the brown rice cake, resulting in a decrease in crumb firmness and an increase in the specific volume. Red rice cakes treated with transglutaminase presented a lower glucose release rate (k) compared to cakes without the enzyme. Cakes from pigmented rice varieties had lower crumb firmness and k values than brown rice cakes. Baking reduced only the contents of ferulic and p-coumaric acids and significantly increased the extractability of hydroxybenzoic, caffeic, caftaric, and protocatechuic acids. However, the addition of the enzyme resulted in a slight decrease in the total phenolic content of the cakes.

Dual modification of potato starch: Effects of heat-moisture and high pressure treatments on starch structure and functionalities.

This study investigated the association of heat moisture treatment (HMT) with high hydrostatic pressure (HHP) and evaluated its effects on the thermal, pasting, swelling power, solubility, morphology, and crystallinity characteristics, as well as in vitro digestibility of potato starch. The single and dual modifications significantly altered the pasting properties of potato starch except for HHP. When HHP was applied to HMT starches, the peak viscosities, setback, and final viscosities were greatly increased compared to those of the samples processed with HMT alone. Dual modification increased the transition temperatures, swelling power, and altered the relative crystallinity. The modified starch exhibited a slower rate of glucose release which decreased proportionally with increasing moisture in the HMT. Dual modification showed a remarkable ability to modify starches with different characteristics and can be used as an alternative in the elaboration of low glycaemic index foods.

Food prototype containing resistant starch type 4 on postprandial glycemic response in healthy adults.

Resistant starch (RS) is a variant of starch that is indigestible by human enzymes and has been acknowledged for multiple physiological benefits including attenuation of postprandial glycemia when incorporated into foods. Distarch phosphate is a RS type 4 (RS4) containing phosphodiester cross-links within and between starch molecules. Considering the importance of RS to human health, the present study aimed to investigate the dose response effect of a novel RS4 (potato-derived distarch phosphate - (VERSAFIBE 1490™) on acute postprandial glycemic responses compared with energy/available carbohydrate and sugar-matched control. The study was designed as a controlled, single-center randomized, single-blinded, cross-over trial, in which 31 healthy adults consumed a baked breakfast cereal bar containing 0, 10 or 20 g RS4 followed by serial blood samples over two hours to determine glucose and insulin concentrations and calculate the incremental area under the curve (iAUC). Results suggest that the addition of RS4 did not reduce iAUC glucose or insulin responses significantly (P > 0.05) at the doses provided. No significant changes in the glucose or insulin maximum concentration (Cmax) and time to reach maximal glucose and insulin concentrations (Tmax) were observed (P > 0.05). Overall, this particular RS4 did not affect measures of glycemia in healthy individuals at doses provided in ready-to-eat baked-good.