Limited information exists regarding the effects of light pearling on the properties of physical grain characteristics, composition, and technological and sensory properties of selected varieties of Western Canadian barley especially hulless barley genotypes with modified starch characteristics. Nine barley genotypes with different hull (hulled and hulless) and starch characteristics (normal, waxy, and high amylose (HA)) were pearled to three differing levels. Scanning electron micrographs showed that the pericarp, testa, aleurone, and subaleurone layers were completely removed in heavily pearled barley whereas only a few outer layers were removed in minimally pearled barley. Waxy starch genotype Fibar and HA starch genotypes, SH99250 & SB94893 contained high levels of soluble β-glucan (9-11%). Waxy starch genotypes exhibited higher β-glucan solubility when cooked compared to normal and HA starch genotypes. However, HA starch genotypes had lower in vitro starch digestibility which may provide a lower glycemic response in humans.

Limited information exists regarding the effects of light pearling on the properties of physical grain characteristics, composition, and technological and sensory properties of selected varieties of Western Canadian barley especially hulless barley genotypes with modified starch characteristics. Nine barley genotypes with different hull (hulled and hulless) and starch characteristics (normal, waxy, and high amylose (HA)) were pearled to three differing levels. Scanning electron micrographs showed that the pericarp, testa, aleurone, and subaleurone layers were completely removed in heavily pearled barley whereas only a few outer layers were removed in minimally pearled barley. Waxy starch genotype Fibar and HA starch genotypes, SH99250 & SB94893 contained high levels of soluble β-glucan (9-11%). Waxy starch genotypes exhibited higher β-glucan solubility when cooked compared to normal and HA starch genotypes. However, HA starch genotypes had lower in vitro starch digestibility which may provide a lower glycemic response in humans.

Omega-3 polyunsaturated fatty acids (ω3 PUFAs) provide important health benefits, but dietary consumption is low. Supplementing foods with ω3 PUFAs is of interest, but intervention strategies are necessary to preserve the integrity of these unstable compounds. Microencapsulation of ω3 PUFA sources is one means of improving their stability. In this work, ω3 PUFA microcapsules were prepared by spray drying with chitosan and blends of chitosan, high-amylose starch, and pullulan as wall materials. The primary objectives of this research were (1) to evaluate the effect of chitosan type and oil:wall ratio on ω3 PUFA microcapsule properties, (2) to evaluate the effect of blending chitosan with high-amylose starch and pullulan on ω3 PUFA microcapsule properties, and (3) to evaluate the oxidative stability of ω3 PUFA microcapsules by monitoring primary and secondary oxidation products during storage. Microcapsule encapsulation efficiencies (EE) ranged from 63% to 79% with the highest EEs observed for microcapsules prepared from chitosan with higher degree of deacetylation (DD) and lower molecular weight (MW). Median microcapsule size ranged from 3 μm to 11 μm. Moisture contents were all below 7% and water activities (a_w) were below 0.27. Microcapsules prepared from blends of chitosan with starch and/or pullulan had lower aw values than those prepared from chitosan alone. Oxidative stability was evaluated by measuring oxidation induction time (OIT) using pressure differential scanning calorimetry. OIT values ranged from 14 to 20 minutes. Microcapsules prepared from chitosan with lower DD and higher MW had longer OITs than those prepared from chitosan with higher DD and lower MW. Microcapsules prepared from blends of chitosan, starch, and pullulan had longer OITs than those prepared from chitosan alone. Oxidative stability of microcapsules during long term storage was evaluated on one microcapsule formulation by monitoring peroxide value (PV) and secondary oxidation products by HS-SPMEGC/ MS. Volatiles including propanal, 1-penten-3-ol, pentanal, hexanal, and 2,4-heptadienal were detected in the headspace of the microcapsules; however, PVs did not indicate substantial oxidation of the ω3-PUFA source during 5 weeks of storage. Chitosan, high-amylose starch, and pullulan are effective materials for microencapsulation of ω3 PUFA sources. / Ph. D.

Les amidons non modifiées et modifiés représentent un groupe d’excipients biodégradables et abondants particulièrement intéressant. Ils ont été largement utilisés en tant qu’excipients à des fins diverses dans des formulations de comprimés, tels que liants et/ou agents de délitement. Le carboxyméthylamidon sodique à haute teneur en amylose atomisé (SD HASCA) a été récemment proposé comme un excipient hydrophile à libération prolongée innovant dans les formes posologiques orales solides. Le carboxyméthylamidon sodique à haute teneur en amylose amorphe (HASCA) a d'abord été produit par l'éthérification de l'amidon de maïs à haute teneur en amylose avec le chloroacétate. HASCA a été par la suite séché par atomisation pour obtenir le SD HASCA. Ce nouvel excipient a montré des propriétés présentant certains avantages dans la production de formes galéniques à libération prolongée. Les comprimés matriciels produits à partir de SD HASCA sont peu coûteux, simples à formuler et faciles à produire par compression directe. Le principal objectif de cette recherche était de poursuivre le développement et l'optimisation des comprimés matriciels utilisant SD HASCA comme excipient pour des formulations orales à libération prolongée. A cet effet, des tests de dissolution simulant les conditions physiologiques du tractus gastro-intestinal les plus pertinentes, en tenant compte de la nature du polymère à l’étude, ont été utilisés pour évaluer les caractéristiques à libération prolongée et démontrer la performance des formulations SD HASCA. Une étude clinique exploratoire a également été réalisée pour évaluer les propriétés de libération prolongée de cette nouvelle forme galénique dans le tractus gastro-intestinal. Le premier article présenté dans cette thèse a évalué les propriétés de libération prolongée et l'intégrité physique de formulations contenant un mélange comprimé de principe actif, de chlorure de sodium et de SD HASCA, dans des milieux de dissolution biologiquement pertinentes. L'influence de différentes valeurs de pH acide et de temps de séjour dans le milieu acide a été étudiée. Le profil de libération prolongée du principe actif à partir d'une formulation de SD HASCA optimisée n'a pas été significativement affecté ni par la valeur de pH acide ni par le temps de séjour dans le milieu acide. Ces résultats suggèrent une influence limitée de la variabilité intra et interindividuelle du pH gastrique sur la cinétique de libération à partir de matrices de SD HASCA. De plus, la formulation optimisée a gardé son intégrité pendant toute la durée des tests de dissolution. L’étude in vivo exploratoire a démontré une absorption prolongée du principe actif après administration orale des comprimés matriciels de SD HASCA et a montré que les comprimés ne se sont pas désintégrés en passant par l'estomac et qu’ils ont résisté à l’hydrolyse par les α-amylases dans l'intestin. Le deuxième article présente le développement de comprimés SD HASCA pour une administration orale une fois par jour et deux fois par jour contenant du chlorhydrate de tramadol (100 mg et 200 mg). Ces formulations à libération prolongée ont présenté des valeurs de dureté élevées sans nécessiter l'ajout de liants, ce qui facilite la production et la manipulation des comprimés au niveau industriel. La force de compression appliquée pour produire les comprimés n'a pas d'incidence significative sur les profils de libération du principe actif. Le temps de libération totale à partir de comprimés SD HASCA a augmenté de manière significative avec le poids du comprimé et peut, de ce fait, être utilisé pour moduler le temps de libération à partir de ces formulations. Lorsque les comprimés ont été exposés à un gradient de pH et à un milieu à 40% d'éthanol, un gel très rigide s’est formé progressivement sur leur surface amenant à la libération prolongée du principe actif. Ces propriétés ont indiqué que SD HASCA est un excipient robuste pour la production de formes galéniques orales à libération prolongée, pouvant réduire la probabilité d’une libération massive de principe actif et, en conséquence, des effets secondaires, même dans le cas de co-administration avec une forte dose d'alcool. Le troisième article a étudié l'effet de α-amylase sur la libération de principe actif à partir de comprimés SD HASCA contenant de l’acétaminophène et du chlorhydrate de tramadol qui ont été développés dans les premières étapes de cette recherche (Acetaminophen SR et Tramadol SR). La modélisation mathématique a montré qu'une augmentation de la concentration d’α-amylase a entraîné une augmentation de l'érosion de polymère par rapport à la diffusion de principe actif comme étant le principal mécanisme contrôlant la libération de principe actif, pour les deux formulations et les deux temps de résidence en milieu acide. Cependant, même si le mécanisme de libération peut être affecté, des concentrations d’α-amylase allant de 0 UI/L à 20000 UI/L n'ont pas eu d'incidence significative sur les profils de libération prolongée à partir de comprimés SD HASCA, indépendamment de la durée de séjour en milieu acide, le principe actif utilisé, la teneur en polymère et la différente composition de chaque formulation. Le travail présenté dans cette thèse démontre clairement l'utilité de SD HASCA en tant qu'un excipient à libération prolongée efficace. / Unmodified and modified starches represent a particularly interesting group of biodegradable and abundant excipients. They have been widely used as excipients for various purposes in tablet formulations, such as binders and/or disintegrants. Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) was recently proposed as an innovating hydrophilic excipient for sustained-release (SR) in solid oral dosage forms. Amorphous high-amylose sodium carboxymethyl starch (HASCA) was first produced by the etherification of high-amylose corn starch with chloroacetate. HASCA was then spray dried to obtain SD HASCA. This new excipient has shown advantageous and effective properties in the production of SR delivery systems. SR matrix tablets prepared from SD HASCA are inexpensive, simple to formulate and easy to produce by direct compression. The main objective of the present research was to continue the development and optimization of matrix tablets using SD HASCA as the retarding excipient in view of their ultimate application as sustained drug-release delivery systems for oral administration. For this purpose, dissolution tests simulating some of the most relevant physiological conditions of the gastrointestinal tract, taking into account the nature of the polymer under investigation, were employed to evaluate the drug-release characteristics and demonstrate the performance of SD HASCA SR formulations. An exploratory clinical study was also carried out to evaluate the SR properties of this new drug delivery system in the gastrointestinal tract. The first article presented in this thesis evaluated the drug-release characteristics and the physical integrity of formulations containing a compressed blend of drug, sodium chloride and SD HASCA in biorelevant media. The influence of different acidic pH values and residence times was investigated. The SR profile from an optimized SD HASCA formulation was not significantly affected by both the acidic pH value and the residence time in the acidic medium. These results suggest a limited influence of intra- and inter-subject variability of gastric pH on the release kinetics from SD HASCA matrices. In addition, the optimized formulation maintained its integrity throughout the duration of the dissolution tests. The exploratory in vivo study demonstrated extended drug absorption after oral administration of SD HASCA matrix tablets and that the matrix tablets did not disintegrate while passing through the stomach and resisted hydrolysis by α-amylase in the intestine. The second article reports the development of once-daily and twice-daily SD HASCA tablets containing tramadol hydrochloride (100 mg and 200 mg). These SR formulations presented high crushing strengths without requiring the addition of binders, which facilitates tablet processing and handling. The compression force (CF) applied to produce the tablets did not significantly affect the drug-release profiles. The total release time from SD HASCA tablets increased significantly in function of the tablet weight and can be used to modulate the total release time from theses formulations. When exposed to a pH gradient and to a 40% ethanol medium, a very rigid gel formed progressively on the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA is a robust excipient for oral, sustained drug-release, likely to minimize the possibility of dose dumping and consequent adverse effects, even when co-administered with high doses of alcohol. The third article investigated the effect of α-amylase on drug-release from previously developed SD HASCA tablets containing acetaminophen and tramadol hydrochloride (Acetaminophen SR and Tramadol SR). Mathematical modeling showed that an increase in α-amylase concentration resulted in an increase of polymer erosion over drug diffusion as the main mechanism controlling drug-release, for both formulations and both residence times in acidic medium. However, even if the mechanism of release was affected, α-amylase concentrations ranging from 0 IU/L to 20000 IU/L did not significantly affect the drug-release profiles from SD HASCA SR tablets, regardless of the residence time in acidic medium, the drug used, the polymer content and the different composition of each formulation. The work presented in this thesis clearly demonstrates the value of SD HASCA as an efficient SR excipient.

Regular starches contain two principal types of glucan polymers: amylopectin and amylose. The structure of amylopectin is characterized according to the unit chain length profile and the nature of the branching pattern, which determine the alignment of glucan chains during biosynthesis. The organization of glucan chains in amylopectin and their impact on the structure of starch are still open to debate. The location of amylose and its exact contribution to the assembly of crystalline lamellae in regular and high-amylose starch granules also remain unknown. The primary focus of this thesis is the organization and flexibility of glucan chains in crystalline lamellae. The organization and flexibility of glucan chains in native, annealed (ANN), and heat-moisture treated (HMT) normal, waxy, hylon V, hylon VII, and hylon VIII corn starches were examined. This study has shown for the first time that increased amounts of apparent amylose in B-type starches hinder the polymorphic transition (from B to A+B) during HMT. The research has also demonstrated that an iodine-glucan complex transformed the B-type polymorphic pattern of hylon starches into a V-type pattern. The differential scanning calorimetry (DSC) results showed that ANN- and HMT-induced changes were most pronounced in hylon starches. These findings suggest that the glucan tie chains influences the assembly of crystalline lamellae in high-amylose starches. The relationship between the internal unit chain composition of amylopectin, and the thermal properties and annealing of starches from four different structural types of amylopectin was investigated by DSC. The onset gelatinization temperature (To) correlated negatively with the number of building blocks in clusters (NBbl) and positively with the inter-block chain length (IB-CL). The enthalpy of gelatinization (∆H) correlated positively with the external chain length of amylopectin. Annealing results showed that starches with a short IB-CL were most susceptible to ANN, as evidenced by a greater increase in the To and Tm. The increase in enthalpy was greater in starches with long external chains and IB-CLs. These data suggest that the internal organization of glucan chains in amylopectin determines the alignment of chains within the crystalline lamellae and thereby the thermal properties and annealing of the starch granules.