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.

Controlled release systems aim at achieving a predictable and reproducible drug release profile over a desired time period. These controlled release formulations offer many advantages over conventional dosage forms. These advantages include: reduced dosing intervals, constant drug levels in the blood, increased patient compliance and decreased adverse effects. Complex controlled release formulations such as those with sustained release properties, often require additional steps during the production phase. The cost and economic impact associated with these complex controlled release dosage formulations often outweigh the short term 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 often equally dispersed throughout a polymer matrix. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of drug release can be controlled by interfering with the amount of swelling and rate of diffusion by manipulating the viscosity of the polymer matrix. Chitosan is an ideal candidate for controlled drug delivery through matrix release systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce fluctuation in peak plasma, and minimize potential side effects without lowering drug bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug. Chitosan beads and excipient containing chitosan beads were prepared by ionotropic gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced. The excipients were added individually and in combinations to the chitosadpyrazinamide dispersion and the beads were characterized on the basis of their morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well as drug release (dissolution properties). The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was noted that the inclusion of excipients in the beads resulted in an increase in drug loading with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of 67.09 ± 0.22%. It was expected that the addition of the pharmaceutical excipients would lead to a sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15 minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug (approximately 40%) in the beads to be released over the extended period. Other polymers can also be investigated to control the release of pyrazinamide. Further studies are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Chitosan has proven through the years as a versatile biomaterial to be used in pharmaceutical applications. Its mucoadhesive properties as well as its ability to manipulate the tight junctions in epithelium membranes have qualified it as an effective drug carrier in controlled drug delivery systems. Microparticles or beads as they are forward called in this study have advantages over conventional drug dosage forms because of a large surface to volume ratio and have the ability to target a specific site for drug release. Indomethacin is an anti-inflammatory drug that causes gastrointestinal side effects in conventional immediate-release dosage forms. The goal is to manipulate the drug delivery vehicle to target the intestines/colon as the site for drug delivery and to minimize this side effect. Thus chitosan beads have been chosen as a drug delivery system for indomethacin in this study. Chitosan beads have been prepared through the ionotropic gelation method using tripolyphophate (TPP) as a cross-linking agent. To prepare the most effective bead to encapsulate indomethacin different formulation and system variables (pH of the TPP solution, the concentration of the TPP solution as well as the indomethacin concentration) have been evaluated according to the following parameters: morphology, drug loading capacity and swelling capability. The ideal pH of the TPP solution was determined at 8.7 and the most effective TPP and indomethacin concentration were 5% w/v and 4% w/v respectively. The chitosan concentration was kept at 3% w/v throughout the study. These concentrations were used to examine the effect of pharmaceutical excipients on the indomethacin release from chitosan beads. The effect of the different excipients namely, ExplotabⒽ(0.25% w/v), Ac-Di-SolⓀ (0.5% w/v) and Vitamin C (0.25% w/v), on the morphology, drug loading capacity, swelling capability as well as the drug release of indomethacin chitosan beads (ICB's) were also studied. The excipients were used in the individually above mentioned concentrations and in combination with each other in the same concentrations. These formulations were used in dissolution studies over a period of 6 hours in PBS pH 7.4 solutions. The indomethacin release rate increased when an excipient was added to the formulation and it dramatically increased when the excipients were added in their various combinations, compared to the formulation that did not contain excipients. / Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Controlled release systems aim at achieving a predictable and reproducible drug release over a desired time period. These systems allow reduced dosing frequency, constant drug levels in the blood, increased patient compliance and decreased adverse effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride, have shown a potential in the delivery of rifampicin. However, because of inadequate amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical excipients to increase the swelling behaviour of the beads to improve drug release, was considered in this study. Chitosan beads were prepared through ionotropic gelation with tripolyphosphate (TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads Explotab®, Ac-Di-Sol® and vitamin C 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. Swelling and morphology studies were used in the evaluation of the different formulations. The swelling and morphology results were then used to select a set of combination and concentrations of two excipients sand then prepare and characterise beads containing two combinations. The combination formulations and formulations containing single excipients were then loaded with rifampicin. Pure chitosan beads exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading capacity of 41.61 % exhibited by chitosan beads containing a combination of Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity ranged within 48 and 63 %. These formulations were used for dissolution studies over a period of 6 hours at pH 5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both pH values. A significant amount of rifampicin was, however, released from the beads, especially at pH 7.40. chitosan beads containing vitamin C also exhibited high rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations and this makes vitamin C a potential excipient for enhanced drug release over a wide pH range (both acidic and alkalinic). However, further studies are necessary to optimise the preparation method to minimise drug loss during loading and to improve the drug loading capacity of the beads. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Chitosan has proven through the years as a versatile biomaterial to be used in pharmaceutical applications. Its mucoadhesive properties as well as its ability to manipulate the tight junctions in epithelium membranes have qualified it as an effective drug carrier in controlled drug delivery systems. Microparticles or beads as they are forward called in this study have advantages over conventional drug dosage forms because of a large surface to volume ratio and have the ability to target a specific site for drug release. Indomethacin is an anti-inflammatory drug that causes gastrointestinal side effects in conventional immediate-release dosage forms. The goal is to manipulate the drug delivery vehicle to target the intestines/colon as the site for drug delivery and to minimize this side effect. Thus chitosan beads have been chosen as a drug delivery system for indomethacin in this study. Chitosan beads have been prepared through the ionotropic gelation method using tripolyphophate (TPP) as a cross-linking agent. To prepare the most effective bead to encapsulate indomethacin different formulation and system variables (pH of the TPP solution, the concentration of the TPP solution as well as the indomethacin concentration) have been evaluated according to the following parameters: morphology, drug loading capacity and swelling capability. The ideal pH of the TPP solution was determined at 8.7 and the most effective TPP and indomethacin concentration were 5% w/v and 4% w/v respectively. The chitosan concentration was kept at 3% w/v throughout the study. These concentrations were used to examine the effect of pharmaceutical excipients on the indomethacin release from chitosan beads. The effect of the different excipients namely, ExplotabⒽ(0.25% w/v), Ac-Di-SolⓀ (0.5% w/v) and Vitamin C (0.25% w/v), on the morphology, drug loading capacity, swelling capability as well as the drug release of indomethacin chitosan beads (ICB's) were also studied. The excipients were used in the individually above mentioned concentrations and in combination with each other in the same concentrations. These formulations were used in dissolution studies over a period of 6 hours in PBS pH 7.4 solutions. The indomethacin release rate increased when an excipient was added to the formulation and it dramatically increased when the excipients were added in their various combinations, compared to the formulation that did not contain excipients. / Contents: Chitosan -- Controlled drug delivery -- Indomethacin -- Inotropic gelation -- Tripolyphosphate (TPP) -- Explotab® -- Ac-Di-Sol® -- Vitamin C / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Controlled release systems aim at achieving a predictable and reproducible drug release over a desired time period. These systems allow reduced dosing frequency, constant drug levels in the blood, increased patient compliance and decreased adverse effects. In a recent study, Chitosan beads, containing N-trimethyl Chitosan chloride, have shown a potential in the delivery of rifampicin. However, because of inadequate amounts of rifampicin released over 24 hours, incorporation of other pharmaceutical excipients to increase the swelling behaviour of the beads to improve drug release, was considered in this study. Chitosan beads were prepared through ionotropic gelation with tripolyphosphate (TPP) as a crosslinking agent. To increase the porosity if the Chitosan beads Explotab®, Ac-Di-Sol® and vitamin C 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. Swelling and morphology studies were used in the evaluation of the different formulations. The swelling and morphology results were then used to select a set of combination and concentrations of two excipients sand then prepare and characterise beads containing two combinations. The combination formulations and formulations containing single excipients were then loaded with rifampicin. Pure chitosan beads exhibited a higher drug loading capacity (67.49 %) compared to the lowest loading capacity of 41.61 % exhibited by chitosan beads containing a combination of Explotab®, Ac-Di-Sol®.For all the other formulations the drug loading capacity ranged within 48 and 63 %. These formulations were used for dissolution studies over a period of 6 hours at pH 5.60 and 7.40. The dissolution results showed that no chitosan has dissolved at both pH values. A significant amount of rifampicin was, however, released from the beads, especially at pH 7.40. chitosan beads containing vitamin C also exhibited high rifampicin release (48.34 ± 1.00) %) at pH 5.60 compared to the other formulations and this makes vitamin C a potential excipient for enhanced drug release over a wide pH range (both acidic and alkalinic). However, further studies are necessary to optimise the preparation method to minimise drug loss during loading and to improve the drug loading capacity of the beads. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

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.

Controlled release systems aim at achieving a predictable and reproducible drug release profile over a desired time period. These controlled release formulations offer many advantages over conventional dosage forms. These advantages include: reduced dosing intervals, constant drug levels in the blood, increased patient compliance and decreased adverse effects. Complex controlled release formulations such as those with sustained release properties, often require additional steps during the production phase. The cost and economic impact associated with these complex controlled release dosage formulations often outweigh the short term 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 often equally dispersed throughout a polymer matrix. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of drug release can be controlled by interfering with the amount of swelling and rate of diffusion by manipulating the viscosity of the polymer matrix. Chitosan is an ideal candidate for controlled drug delivery through matrix release systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce fluctuation in peak plasma, and minimize potential side effects without lowering drug bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug. Chitosan beads and excipient containing chitosan beads were prepared by ionotropic gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced. The excipients were added individually and in combinations to the chitosadpyrazinamide dispersion and the beads were characterized on the basis of their morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well as drug release (dissolution properties). The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was noted that the inclusion of excipients in the beads resulted in an increase in drug loading with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of 67.09 ± 0.22%. It was expected that the addition of the pharmaceutical excipients would lead to a sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15 minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug (approximately 40%) in the beads to be released over the extended period. Other polymers can also be investigated to control the release of pyrazinamide. Further studies are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.