Formulations that are able to control the release of drug have become an integral part of the pha... more Formulations that are able to control the release of drug have become an integral part of the pharmaceutical industry. In particular oral drug delivery has been the focus of pharmaceutical research for many years. This type of drug delivery has been at the centre of research due to its many benefits over conventional dosage. The focus of this review is on matrix tablets due to their widely use and simplicity of the formulation. This includes the discussion of various types of matrix tablets and factors affecting the drug release from these formulations. The mechanism of drug release from HPMC matrices is also discussed.
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.
Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipien... more Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.
In this article, the influence of agitation in descending and ascending sequences as a systematic... more In this article, the influence of agitation in descending and ascending sequences as a systematic method development process for potentially discriminating fed and fasted states and evaluation of its effects on the drug release from swelling gel-forming hydrophilic matrix tablets were investigated. Theophylline 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 at 5, 10, 15, 20, 25 and 30 dips per minute (dpm). Agitation had a profound effect on the drug release from the HPMC K100LV matrices. Drug release in pH 1.2 changed from about 40% at 5 dpm to about 80% at 30 dpm over a 60 min period alone. The matrices containing HPMC K4M, K15M and K100M however were not significantly affected by the agitation rate. The similarity factor f2 was calculated using drug release at 10 dpm as a reference. The ascending agitations of 5-30 dpm and the descending order of agitation 30-5 dpm were also evaluated. Anomalous transport was the only kinetic of release for the K4M, K15M and K100M tablet matrices. The lower viscous polymer of K100LV had some matrices exhibiting Fickian diffusion as its kinetics of release. The use of systematic change of agitation method may indicate potential fed and fasted effects on drug release from hydrophilic matrices.
... Kofi Asare-Addo a , Marina Levina b , Ali R. Rajabi-Siahboomi b and Ali Nokhodchi a , Corresp... more ... Kofi Asare-Addo a , Marina Levina b , Ali R. Rajabi-Siahboomi b and Ali Nokhodchi a , Corresponding Author Contact Information , E-mail The Corresponding Author. a Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, Kent, UK. ...
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.
Formulations that are able to control the release of drug have become an integral part of the pha... more Formulations that are able to control the release of drug have become an integral part of the pharmaceutical industry. In particular oral drug delivery has been the focus of pharmaceutical research for many years. This type of drug delivery has been at the centre of research due to its many benefits over conventional dosage. The focus of this review is on matrix tablets due to their widely use and simplicity of the formulation. This includes the discussion of various types of matrix tablets and factors affecting the drug release from these formulations. The mechanism of drug release from HPMC matrices is also discussed.
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.
Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipien... more Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.
In this article, the influence of agitation in descending and ascending sequences as a systematic... more In this article, the influence of agitation in descending and ascending sequences as a systematic method development process for potentially discriminating fed and fasted states and evaluation of its effects on the drug release from swelling gel-forming hydrophilic matrix tablets were investigated. Theophylline 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 at 5, 10, 15, 20, 25 and 30 dips per minute (dpm). Agitation had a profound effect on the drug release from the HPMC K100LV matrices. Drug release in pH 1.2 changed from about 40% at 5 dpm to about 80% at 30 dpm over a 60 min period alone. The matrices containing HPMC K4M, K15M and K100M however were not significantly affected by the agitation rate. The similarity factor f2 was calculated using drug release at 10 dpm as a reference. The ascending agitations of 5-30 dpm and the descending order of agitation 30-5 dpm were also evaluated. Anomalous transport was the only kinetic of release for the K4M, K15M and K100M tablet matrices. The lower viscous polymer of K100LV had some matrices exhibiting Fickian diffusion as its kinetics of release. The use of systematic change of agitation method may indicate potential fed and fasted effects on drug release from hydrophilic matrices.
... Kofi Asare-Addo a , Marina Levina b , Ali R. Rajabi-Siahboomi b and Ali Nokhodchi a , Corresp... more ... Kofi Asare-Addo a , Marina Levina b , Ali R. Rajabi-Siahboomi b and Ali Nokhodchi a , Corresponding Author Contact Information , E-mail The Corresponding Author. a Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, Kent, UK. ...
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.
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