Controlled release formulations offer many advantages over conventional dosage forms. These include reduced plasma fluctuations and improved patient comp1i:nce. Complex controlled release formulations such as those with enteric release properties, often require additional steps in the production phase. The costs and economic impact associated with these complex controlled release dosage formulations often outweigh the immediate benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations, the drug is generally dispersed throughout a polymer matrix. The rate of drug release is often determined by the viscosity or complexity of the polymer matrix through which the drug needs to diffuse in order to be released. With enteric release the polymer coating, insoluble in an acidic environment is often applied in the final phase of production. Chitosan is a versatile polymer of natural origin with many favourable characteristics. These include its safety, biocompatibility, and biodegradability. Simple methods can be applied and modified to produce controlled release particles form chitosan. The effect of modern controlled release polymers such as Aqoat AS-HF, Eudragit SlOO and Kollidon SR was investigated. Chitosan beads and chitosan-polymer beads, as well as chitosan granules and chitosan-polymer granules, were prepared and investigated as possible controlled release formulations. Ketoprofen was chosen as the model drug. Chitosan beads and chitosan-polymer beads were prepared by inotropic gelation in tripolyphosphate. Chitosan granules and chitosan-polymer matrix granules were prepared by binding chitosan with an acetic acid solution as a granulating system. The beads and granules appeared differed in appearance as well as in the results obtained from various experiments. Granules prepared in the study did not appear to be effective with regards to enteric and controlled release. Beads prepared form Kollidon SR appeared to be effective with regards to enteric and controlled release, with Kollidon 1% and 5% w/v chitosan beads achieving good drug loading of up to 73.13% and releasing less than 15 % of the total drug content in 0.1 M HCI after 60 minutes. Drug release continued steadily for up to 360 minutes in pH 7.2. It was concluded that Kollidon SR loaded chitosan beads nay be a viable controlled release dosage form with enteric release properties, and that future experiments, possibly with lower polymer concentrations, are worthwhile / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.

In controlled release applications a drug is molecularly dispersed in a polymer phase. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of the drug release can be controlled by interfering with the swelling rate of the beads or by influencing diffusion through the viscosity of the polymer. Beads that contain chitosan were prepared through the ionotropic gelation method where tripolyphosphate (TPP) was used as the crosslinking agent. Beads that consisted of 3% w/v isoniazid (lNH) and 5% w/v chitosan were prepared in a 5% w/v TPP solution (pH 8.7) as the primary beads. To improve the drug loading of chitosan isoniazid beads (ClB) the TPP concentration, pH of the TPP solution and the INH concentrations were altered for maximum drug loading. To increase the porosity of the beads of chitosan beads Explotab® (EXPL), Ac-Di-Sol® (ADS) and Vitamin C (VC) were added individually to chitosan solutions at concentrations of 0.1, 0.25 and 0.5% w/v before adding the mixture to the TPP solution. Morphology, swelling and drug loading studies were used to evaluate the different formulations. After these excipients were added individually they were also added in combinations of two excipients respectively and characterised. From the results of the drug loading studies the beads that contained only chitosan and isoniazid showed a percentage drug loading of (43.92%) which is the best of all the beads that were analyzed. The multi excipient combination of Ac-Di-Sol® and Explotab® showed the best swelling capability at both pH levels. Dissolution studies were conducted on all the formu lations over a period of 6 hours (360 minutes) at pH 5.6 and pH 7.4. From the dissolution results it were clear that no chitosan dissolved at both pH values. The dissolution of single pharmaceutical excipient (SPE) and multi pharmaceutical excipient (MPE) formulations can be arranged in the following order: VC/ADS < VC < ADS/EXPL < ADS < VC/EXPL < CIB < EXPL. Explotab® is a potential excipient for enhanced drug release over a wide pH range. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Over the past couple of years there has been rapid progress in the development and design of safe and effective delivery systems for the administration of protein and peptide drugs. The effective delivery of these type of drugs are not always as simple as one may think, due to various inherent characteristics of these compounds. Due to the hydrophilic nature and molecular size of peptide and protein drugs, such as recombinant human growth hormone, they are poorly absorbed across mucosal epithelia, both transcellularly and paracellularly. This problem can be overcome by the inclusion of absorption enhancers in peptide and protein drug formulations but this is not necessarily the best method to follow. This investigation focussed specifically on the evaluation of the ability of the PheroidTM carrier system to transport recombinant human growth hormone across mucosal epithelia especially when administered via the nasal cavity. The PheroidTM delivery system is a patented system consisting of a unique submicron emulsion type formulation. The PheroidTM delivery system, based on PheroidTM technology, will for ease of reading be called Pheroid(s) only throughout the rest of this dissertation. The Pheroid carrier system is a unique microcolloidal drug delivery system. A Pheroid is a stable structure within a novel therapeutic system which can be manipulated in terms of morphology, structure, size and function. Pheroids consist mainly of plant and essential fatty acids and can entrap, transport and deliver pharmacologically active compounds and other useful substances to the desired site of action. The specific objectives of this study can be summarised as follows: a literature study on Pheroid technology; a literature study on chitosan and N-trimethyl chitosan chloride; a literature study on recombinant human growth hormone (somatropin); a literature study on nasal drug administration; formulation of a suitable Pheroid carrier; entrapment of somatropin in the Pheroid carrier, and in vivo evaluation of nasal absorption of somatropin in Sprague-Dawley rats. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

The most useful dosage form taken from a patient's point of view is tablets because of its simplicity and portability (Takeuchi et al., 2004:132). Manufacturing of tablets can be done by wet granulation or direct compression of powders. For direct compression it is important that the powder has good particle flowability and compactability. Various methods to investigate these properties of the powder have been developed, which provide comparative indices to assist in the process and formulation design (Li et al., 2004:77). Chitin is the second most abundant naturally occurring biopolymer after cellulose (Asada et al., 2004: 169). Chitosan is produced by the partial alkaline N-deacetylation of chitin (Berger et al., 2004:36). The structure of chitosan is similar to that of cellulose, an excipient with acceptable compression properties. According to Olsson and Nystrom (2001 :204) hydrogen bonds are considered to be one of the dominating bonding mechanisms for most pharmaceutical powders. The extent of the effect will depend on the particle shape and surface characteristics (Hiestand, 1997:237-241). Considering the structure of chitosan it predicts the ability to form H-bonds, and produce tablets with acceptable mechanical strength. The two major problems identified in terms of the use of chitosan as directly compressible filler in tablet formulations is its poor flow and compressibility properties (Aucamp, 2004; Buys, 2006; De Kock, 2005). During the characterization of chitosan raw material the aim was to determine to which extend its physical properties affects the flow of the material and to compare its flow properties to that of other commonly used tablet fillers. Two batches chitosan were compared to each other to determine the effect of morphology on their physical properties. When ranking the composite index of the powders it was clear that in regards to the other materials used, chitosan was ranked the lowest. These results confirmed the poor flow of chitosan. The characterization of the two chitosan batches used in this study revealed significant differences in the morphology of the particles of the different batches. Because of these large inter-batch variations with respect to the physical properties of the different batches even when manufactured by the same company via the same method, these variations also affected the flow characteristics of the two batches. From the particle characterization in chitosan it could be concluded that the previously observed poor compression characteristics (De Kock, 2005; Aucamp, 2004) could be attributed to the low density and high porosity of the material. Only one of the batches studied could be compressed on a standard eccentric press, which could be attributed to the differences between the physical properties of two batches. Chitosan showed promising compression characteristics at specific machine settings (limited range of upper punch settings), with good crushing strength and low friabifity. The drawbacks of the compression properties for chitosan on the standard press was the relative low tablet weights that could be compressed for a specific die size and the narrow range for the upper punch setting to achieve an acceptable mechanical tablet strength and friability. The results of Buys (2006) showed promising results for chitosan when changing the compression cycle from a single fill to a double die fill for each compression cycle. The advantage of the modified eccentric tablet press in terms of improvement of the compactibility of low density materials was clearly demonstrated by the results from the compression studies of both chitosan batches. With the double fill cycle on the modified press it was possible to fill the die with a sufficient amount of powder to produce acceptable tablets with sufficient crushing strength and low friability. The modified tablet press made it possible to compress the batch (021010) chitosan which couldn't be compressed on the standard tablet press. Batch (030912), which was compressed on the standard as well as the modified press, showed improved results in the crushing strength and friability with increase of the percentage compression setting at a constant upper punch setting. Batch 030912 showed better results than that of batch 021010 and this could be attributed to the physical differences between the two batches. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

The most useful dosage form taken from a patient's point of view is tablets because of its simplicity and portability (Takeuchi et al., 2004:132). Manufacturing of tablets can be done by wet granulation or direct compression of powders. For direct compression it is important that the powder has good particle flowability and compactability. Various methods to investigate these properties of the powder have been developed, which provide comparative indices to assist in the process and formulation design (Li et al., 2004:77). Chitin is the second most abundant naturally occurring biopolymer after cellulose (Asada et al., 2004: 169). Chitosan is produced by the partial alkaline N-deacetylation of chitin (Berger et al., 2004:36). The structure of chitosan is similar to that of cellulose, an excipient with acceptable compression properties. According to Olsson and Nystrom (2001 :204) hydrogen bonds are considered to be one of the dominating bonding mechanisms for most pharmaceutical powders. The extent of the effect will depend on the particle shape and surface characteristics (Hiestand, 1997:237-241). Considering the structure of chitosan it predicts the ability to form H-bonds, and produce tablets with acceptable mechanical strength. The two major problems identified in terms of the use of chitosan as directly compressible filler in tablet formulations is its poor flow and compressibility properties (Aucamp, 2004; Buys, 2006; De Kock, 2005). During the characterization of chitosan raw material the aim was to determine to which extend its physical properties affects the flow of the material and to compare its flow properties to that of other commonly used tablet fillers. Two batches chitosan were compared to each other to determine the effect of morphology on their physical properties. When ranking the composite index of the powders it was clear that in regards to the other materials used, chitosan was ranked the lowest. These results confirmed the poor flow of chitosan. The characterization of the two chitosan batches used in this study revealed significant differences in the morphology of the particles of the different batches. Because of these large inter-batch variations with respect to the physical properties of the different batches even when manufactured by the same company via the same method, these variations also affected the flow characteristics of the two batches. From the particle characterization in chitosan it could be concluded that the previously observed poor compression characteristics (De Kock, 2005; Aucamp, 2004) could be attributed to the low density and high porosity of the material. Only one of the batches studied could be compressed on a standard eccentric press, which could be attributed to the differences between the physical properties of two batches. Chitosan showed promising compression characteristics at specific machine settings (limited range of upper punch settings), with good crushing strength and low friabifity. The drawbacks of the compression properties for chitosan on the standard press was the relative low tablet weights that could be compressed for a specific die size and the narrow range for the upper punch setting to achieve an acceptable mechanical tablet strength and friability. The results of Buys (2006) showed promising results for chitosan when changing the compression cycle from a single fill to a double die fill for each compression cycle. The advantage of the modified eccentric tablet press in terms of improvement of the compactibility of low density materials was clearly demonstrated by the results from the compression studies of both chitosan batches. With the double fill cycle on the modified press it was possible to fill the die with a sufficient amount of powder to produce acceptable tablets with sufficient crushing strength and low friability. The modified tablet press made it possible to compress the batch (021010) chitosan which couldn't be compressed on the standard tablet press. Batch (030912), which was compressed on the standard as well as the modified press, showed improved results in the crushing strength and friability with increase of the percentage compression setting at a constant upper punch setting. Batch 030912 showed better results than that of batch 021010 and this could be attributed to the physical differences between the two batches. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

Diamond is a promising material with unique chemical properties. In this thesis, nano-scale diamond quantum size effects were investigated using several chemical property indicators. The results show that the chemical properties are strongly dependent on size for film thicknesses smaller than 1 nm (1D), and for nanodiamond particle diameters less than 2 nm (3D). When the sizes exceed these ranges there are no longer any quantum effects. The influence of surface termination coverage on the surface chemical properties has been calculated for the 2×1 reconstructed diamond (100) surface and for the diamond (111) surface. The terminating species included COOH and NH2 groups, which both are beneficial for the immobilization of biomolecules. The results of the calculations show that it is energetically possible to terminate the diamond surfaces up to 100% with NH2, while it is only possible to cover the surfaces up to 50% with COOH species. The reason for the latter result is most probably the larger sterical hindrance amongst the adsorbates. Both types of termination species were shown to influence the diamond surface electronic properties (e.g., HOMO/LUMO levels). In order to extend the diamond utility for biomedical applications, especially implant design, interactions of various growth factors with the diamond surfaces were also simulated. For non-solvent diamond-biomolecule systems, the results show that adhesion affinities are strongly dependent on biomolecule molecular weights. When including a water based solvent in the systems, the results show good physisorption affinities between proteins and diamond. Proteins structures, before and after physisorption, were visualized, and further investigated with respect to electrostatic properties and functional groups. By comparing the biomolecular structural changes during the adhesion processes, it can be concluded that both the general structures, as well as the binding pocket structures, were kept intact after the adhesion to the diamond surfaces (regardless of the adhesion affinities). In addition, the surface electronic potential distributions were maintained, which indicate preserved biomolecule functionalities. / Vascubone

The shrimp processing industry has to deal with the ever-growing costs associated with the disposal of their residuals. However, investigation into the possibility of making high-value biopolymers (chitin and chitosan) from this waste shows significant potential for developing a chitin and chitosan industry in Quebec. / The pharmaceutical and medicine industry is the target market for high-grade chitosan. Based on the related data of cellulose derivatives (the closest substitute for chitosan), the Bass model was used to forecast the sales of high-grade chitosan in Quebec. It is estimated that the potential market for chitosan in Quebec is worth 37 million dollars (in 1999 prices) cumulative for the next 20 year period and 59 million for Canada. In the first year of marketing chitosan, sales in Canada (high-grade) are expected to reach $3.2 million from which $1.55 million is expected to be generated in Quebec. (Abstract shortened by UMI.)

Graduation date: 2004

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.) -- Mississippi State University. Dave C. Swalm School of Chemical Engineering. / Title from title screen. Includes bibliographical references.