Release of nicotine from conventional gums and from gums made using a directly compressible gum b... more Release of nicotine from conventional gums and from gums made using a directly compressible gum base was studied using the European Pharmacopoeia apparatus for testing of medicated chewing gums. It was found that gum base and the method of preparation used in a formulation were important factors when controlling the release of drugs from chewing gum.
International journal of pharmaceutics, Jan 8, 2015
The nasal mucosa provides a potentially good route for local and systemic drug delivery. However,... more The nasal mucosa provides a potentially good route for local and systemic drug delivery. However, the protective feature of the nasal cavity make intranasal delivery challenging. The application of mucoadhesive polymers in nasal drug delivery systems enhances the retention of the dosage form in the nasal cavity. Several groups have investigated using low acyl gellan as a drug delivery vehicle but only limited research however, has been performed on high acyl gellan for this purpose, despite its properties being more conducive to mucoadhesion. High acyl gellan produces highly elastic gels below 60°C which make it difficult to spray using a mechanical spray device. Therefore, in this study we have tried to address this problem by making fluid gels by introducing a shear force during gelation of the gellan polymer. These fluid gel systems contain gelled micro-particles suspended in a solution of un-gelled polymer. These systems can therefore behave as pourable viscoelastic fluids. In t...
Oral liquids are often preferred for drug administration to patients for whom swallowing is diffi... more Oral liquids are often preferred for drug administration to patients for whom swallowing is difficult, however, formulating modified release versions can be challenging. A potential route to achieve modified release in oral liquids is by using fluid (sheared) gels formed by introducing a shear field during gelation in gel-forming biopolymers. These fluid gels can act as pourable viscoelastic fluids but retain true gel micro/nano structure. Here, we have demonstrated that fluid gels have potential as paediatric oral liquids preventing release of ibuprofen in simulated gastric fluid. Subsequent release at pH 7.4 was affected by the duration of exposure and magnitude of acid pH with a linear relationship between onset of release and the preceding acidic exposure duration. Delayed release was a result of increasing gel stiffness, a consequence of the acidity of the initial release media and exposure time. A much faster release rate was measured when exposure time in acid was 10 min compared with 60 min. This study highlights the potential to design fluid gels that are tuned to have a specified stiffness at a particular pH and exposure time. This could enable the preparation oral liquids with modified release behaviour.
Hypromellose, HPMC, is frequently used to control drug release from matrix tablet formulations. D... more Hypromellose, HPMC, is frequently used to control drug release from matrix tablet formulations. Drug is released by a combination of diffusion through and erosion of, the matrix and is usually measured invitro by separate dissolution and swelling/erosion studies. The present study was designed to measure matrix erosion, polymer dissolution and drug release kinetics and their inter-relationship in a single experiment using a phenol-sulphuric acid assay to quantify dissolved HPMC alongside spectrophotometrical analysis of drug release. HPMC-based matrix tablets were manufactured containing two drugs at various drug:HPMC ratios. Drug release was determined and the degree of erosion was calculated by gravimetry. Results showed the matrix erosion rate and drug release were dependent on HPMC content and drug solubility, as expected. It was also apparent that the erosion rate was directly related to the drug release kinetics and comparative analysis of both matrix erosion techniques showed a high level of correlation. The findings show that a simple and inexpensive assay can be utilised not only to quantify HPMC but can also be used to calculate the degree of erosion of tablet matrices, negating the need for a separate study and providing a simplified practical approach that may be of use during product optimization.
The evaluation of the effects of different media ionic strengths and pH on the release of hydroch... more The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic strength of the media was varied over a range of 0-0.4M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices.
Salt formation is an effective method of improving physicochemical properties of acidic and basic... more Salt formation is an effective method of improving physicochemical properties of acidic and basic drugs. The selection of a salt form most suitable for drug development requires a well-designed screening strategy to ensure various issues are addressed in the early development stages. Triboelectrification of pharmaceutical powders may cause problems during processing such as segregation of components due to the effects of particle adhesion. However, very little work has been done on the effect of salt formation on triboelectrification properties. In this paper, salts of flurbiprofen were prepared by combining the drug with a selection of closely related amine counter ions. The aim of the work was to investigate the impact of the counter ion on electrostatic charge of the resultant salts to inform the salt selection process. The experimental results show the magnitude of charge and polarity of the flurbiprofen salts to be highly dependent on the type of counter ion selected for the salt formation. Furthermore, particle adhesion to the stainless steel surface of the shaking container and the salts' compression properties were measured. The formed salts had lower electrostatic charges, improved tabletability, and resulted in reduced adhesion of these powders compared with the parent drug.
Release of nicotine from conventional gums and from gums made using a directly compressible gum b... more Release of nicotine from conventional gums and from gums made using a directly compressible gum base was studied using the European Pharmacopoeia apparatus for testing of medicated chewing gums. It was found that gum base and the method of preparation used in a formulation were important factors when controlling the release of drugs from chewing gum.
International journal of pharmaceutics, Jan 8, 2015
The nasal mucosa provides a potentially good route for local and systemic drug delivery. However,... more The nasal mucosa provides a potentially good route for local and systemic drug delivery. However, the protective feature of the nasal cavity make intranasal delivery challenging. The application of mucoadhesive polymers in nasal drug delivery systems enhances the retention of the dosage form in the nasal cavity. Several groups have investigated using low acyl gellan as a drug delivery vehicle but only limited research however, has been performed on high acyl gellan for this purpose, despite its properties being more conducive to mucoadhesion. High acyl gellan produces highly elastic gels below 60°C which make it difficult to spray using a mechanical spray device. Therefore, in this study we have tried to address this problem by making fluid gels by introducing a shear force during gelation of the gellan polymer. These fluid gel systems contain gelled micro-particles suspended in a solution of un-gelled polymer. These systems can therefore behave as pourable viscoelastic fluids. In t...
Oral liquids are often preferred for drug administration to patients for whom swallowing is diffi... more Oral liquids are often preferred for drug administration to patients for whom swallowing is difficult, however, formulating modified release versions can be challenging. A potential route to achieve modified release in oral liquids is by using fluid (sheared) gels formed by introducing a shear field during gelation in gel-forming biopolymers. These fluid gels can act as pourable viscoelastic fluids but retain true gel micro/nano structure. Here, we have demonstrated that fluid gels have potential as paediatric oral liquids preventing release of ibuprofen in simulated gastric fluid. Subsequent release at pH 7.4 was affected by the duration of exposure and magnitude of acid pH with a linear relationship between onset of release and the preceding acidic exposure duration. Delayed release was a result of increasing gel stiffness, a consequence of the acidity of the initial release media and exposure time. A much faster release rate was measured when exposure time in acid was 10 min compared with 60 min. This study highlights the potential to design fluid gels that are tuned to have a specified stiffness at a particular pH and exposure time. This could enable the preparation oral liquids with modified release behaviour.
Hypromellose, HPMC, is frequently used to control drug release from matrix tablet formulations. D... more Hypromellose, HPMC, is frequently used to control drug release from matrix tablet formulations. Drug is released by a combination of diffusion through and erosion of, the matrix and is usually measured invitro by separate dissolution and swelling/erosion studies. The present study was designed to measure matrix erosion, polymer dissolution and drug release kinetics and their inter-relationship in a single experiment using a phenol-sulphuric acid assay to quantify dissolved HPMC alongside spectrophotometrical analysis of drug release. HPMC-based matrix tablets were manufactured containing two drugs at various drug:HPMC ratios. Drug release was determined and the degree of erosion was calculated by gravimetry. Results showed the matrix erosion rate and drug release were dependent on HPMC content and drug solubility, as expected. It was also apparent that the erosion rate was directly related to the drug release kinetics and comparative analysis of both matrix erosion techniques showed a high level of correlation. The findings show that a simple and inexpensive assay can be utilised not only to quantify HPMC but can also be used to calculate the degree of erosion of tablet matrices, negating the need for a separate study and providing a simplified practical approach that may be of use during product optimization.
The evaluation of the effects of different media ionic strengths and pH on the release of hydroch... more The evaluation of the effects of different media ionic strengths and pH on the release of hydrochlorothiazide, a poorly soluble drug, and diltiazem hydrochloride, a cationic and soluble drug, from a gel forming hydrophilic polymeric matrix was the objective of this study. The drug to polymer ratio of formulated tablets was 4:1. Hydrochlorothiazide or diltiazem HCl extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The ionic strength of the media was varied over a range of 0-0.4M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. Sodium chloride was used for ionic regulation due to its ability to salt out polymers in the midrange of the lyotropic series. The results showed that the ionic strength had a profound effect on the drug release from the diltiazem HCl K100LV matrices. The K4M, K15M and K100M tablets however withstood the effects of media ionic strength and showed a decrease in drug release to occur with an increase in ionic strength. For example, drug release after the 1h mark for the K100M matrices in water was 36%. Drug release in pH 1.2 after 1h was 30%. An increase of the pH 1.2 ionic strength to 0.4M saw a reduction of drug release to 26%. This was the general trend for the K4M and K15M matrices as well. The similarity factor f2 was calculated using drug release in water as a reference. Despite similarity occurring for all the diltiazem HCl matrices in the pH 1.2 media (f2=64-72), increases of ionic strength at 0.2M and 0.4M brought about dissimilarity. The hydrochlorothiazide tablet matrices showed similarity at all the ionic strength tested for all polymers (f2=56-81). The values of f2 however reduced with increasing ionic strengths. DSC hydration results explained the hydrochlorothiazide release from their HPMC matrices. There was an increase in bound water as ionic strengths increased. Texture analysis was employed to determine the gel strength and also to explain the drug release for the diltiazem hydrochloride. This methodology can be used as a valuable tool for predicting potential ionic effects related to in vivo fed and fasted states on drug release from hydrophilic ER matrices.
Salt formation is an effective method of improving physicochemical properties of acidic and basic... more Salt formation is an effective method of improving physicochemical properties of acidic and basic drugs. The selection of a salt form most suitable for drug development requires a well-designed screening strategy to ensure various issues are addressed in the early development stages. Triboelectrification of pharmaceutical powders may cause problems during processing such as segregation of components due to the effects of particle adhesion. However, very little work has been done on the effect of salt formation on triboelectrification properties. In this paper, salts of flurbiprofen were prepared by combining the drug with a selection of closely related amine counter ions. The aim of the work was to investigate the impact of the counter ion on electrostatic charge of the resultant salts to inform the salt selection process. The experimental results show the magnitude of charge and polarity of the flurbiprofen salts to be highly dependent on the type of counter ion selected for the salt formation. Furthermore, particle adhesion to the stainless steel surface of the shaking container and the salts' compression properties were measured. The formed salts had lower electrostatic charges, improved tabletability, and resulted in reduced adhesion of these powders compared with the parent drug.
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