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Permeation of excised intestinal tissue by insulin released from Eudragit® L100/Trimethyl chitosan chloride microspheres /E.B. Marais.Marais, Etienne Barend January 2013 (has links)
The purpose of this research project was to develop and characterise matrix type microspheres prepared from Eudragit® L100, containing insulin as model peptide drug as well as an absorption enhancer, N-trimethyl chitosan chloride (TMC), to improve intestinal absorption via the paracellular route. Insulin loaded microspheres were prepared using a single water in oil emulsification/evaporation method in accordance with a fractional factorial design (23) and subsequently characterised in terms of morphology as well as internal structure. Also, insulin and TMC loading were determined using a high pressure liquid chromatography analysis (HPLC) and colorimetric assay, respectively.
Scanning electron microscopic characterisation revealed that most microsphere formulations showed a spherical shape and smooth surface with a sponge-like internal structure as well as relatively good homogeneity in terms of size distribution. Insulin loading ranged from 27.9 ± 14.25 – 52.4 ± 2.72% between the different formulations. TMC loading was lower than for insulin and ranged from 29.1 ± 3.3 - 37.7 ± 2.3% between the different formulations. The pronounced difference in insulin and TMC loading between the microsphere formulations is probably the result of the multitude parameters involved as well as the complex physicochemical processes which govern emulsification/solvent evaporation. Based on the microsphere characterisation results, two formulations were selected (i.e. B and F) for further characterisation (i.e. particle size distribution, dissolution behaviour, and enteric nature) and for in vitro evaluation of insulin transport across excised Fischer (FSR) rat intestinal tissue using a Sweetana-Grass diffusion chamber. Particle size analysis by means of laser light diffraction of the two selected microsphere formulations revealed that the mean particle size (based on volume) ranged from 135.7 ± 41.05 to 157.3 ± 31.74 m. Dissolution results for microsphere Formulations B and F revealed that both insulin and TMC were released from the microsphere formulations in an alkaline environment (pH 7.4). The mean dissolution time (MDT) for insulin ranged from 34.5 ± 4.01 to 42.6 ± 9.06 min, while the MDT for TMC ranged from 1.2 ± 1.73 to 6.8 ± 6.42 min. Statistical analysis revealed no significant differences in the MDT of either insulin or TMC (p-value > 0.05) between the two formulations, although the difference between insulin and TMC of each formulation was significant (p-value < 0.05). Microsphere formulations B and F released 36.92 and 48.21% of their total drug content over a period of 1 h in 0.1 M HCl.
Microsphere Formulation B showed 8.3 ± 0.52% and formulation F 8.9 ± 2.26% transport of the initial insulin dose after a period of 120 min across excised rat intestinal tissue. The increase in insulin transport by the microsphere formulations compared to that of the control group (i.e. insulin alone) correlated well with the decrease in transepithelial electrical resistance (TEER) caused by the microsphere formulations. The transport of insulin from Formulations B and F represented transport enhancement ratios of 10.67 and 9.68, respectively.
Insulin loaded EudragitL100 microspheres containing TMC were successfully prepared by emulsification/solvent evaporation that demonstrated promising potential to serve as oral drug delivery systems for insulin. The microspheres exhibited improved insulin permeability across intestinal epithelial tissue; however, its enteric properties should be improved and clinical effectiveness need to be confirmed by future in vivo studies. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
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Permeation of excised intestinal tissue by insulin released from Eudragit® L100/Trimethyl chitosan chloride microspheres /E.B. Marais.Marais, Etienne Barend January 2013 (has links)
The purpose of this research project was to develop and characterise matrix type microspheres prepared from Eudragit® L100, containing insulin as model peptide drug as well as an absorption enhancer, N-trimethyl chitosan chloride (TMC), to improve intestinal absorption via the paracellular route. Insulin loaded microspheres were prepared using a single water in oil emulsification/evaporation method in accordance with a fractional factorial design (23) and subsequently characterised in terms of morphology as well as internal structure. Also, insulin and TMC loading were determined using a high pressure liquid chromatography analysis (HPLC) and colorimetric assay, respectively.
Scanning electron microscopic characterisation revealed that most microsphere formulations showed a spherical shape and smooth surface with a sponge-like internal structure as well as relatively good homogeneity in terms of size distribution. Insulin loading ranged from 27.9 ± 14.25 – 52.4 ± 2.72% between the different formulations. TMC loading was lower than for insulin and ranged from 29.1 ± 3.3 - 37.7 ± 2.3% between the different formulations. The pronounced difference in insulin and TMC loading between the microsphere formulations is probably the result of the multitude parameters involved as well as the complex physicochemical processes which govern emulsification/solvent evaporation. Based on the microsphere characterisation results, two formulations were selected (i.e. B and F) for further characterisation (i.e. particle size distribution, dissolution behaviour, and enteric nature) and for in vitro evaluation of insulin transport across excised Fischer (FSR) rat intestinal tissue using a Sweetana-Grass diffusion chamber. Particle size analysis by means of laser light diffraction of the two selected microsphere formulations revealed that the mean particle size (based on volume) ranged from 135.7 ± 41.05 to 157.3 ± 31.74 m. Dissolution results for microsphere Formulations B and F revealed that both insulin and TMC were released from the microsphere formulations in an alkaline environment (pH 7.4). The mean dissolution time (MDT) for insulin ranged from 34.5 ± 4.01 to 42.6 ± 9.06 min, while the MDT for TMC ranged from 1.2 ± 1.73 to 6.8 ± 6.42 min. Statistical analysis revealed no significant differences in the MDT of either insulin or TMC (p-value > 0.05) between the two formulations, although the difference between insulin and TMC of each formulation was significant (p-value < 0.05). Microsphere formulations B and F released 36.92 and 48.21% of their total drug content over a period of 1 h in 0.1 M HCl.
Microsphere Formulation B showed 8.3 ± 0.52% and formulation F 8.9 ± 2.26% transport of the initial insulin dose after a period of 120 min across excised rat intestinal tissue. The increase in insulin transport by the microsphere formulations compared to that of the control group (i.e. insulin alone) correlated well with the decrease in transepithelial electrical resistance (TEER) caused by the microsphere formulations. The transport of insulin from Formulations B and F represented transport enhancement ratios of 10.67 and 9.68, respectively.
Insulin loaded EudragitL100 microspheres containing TMC were successfully prepared by emulsification/solvent evaporation that demonstrated promising potential to serve as oral drug delivery systems for insulin. The microspheres exhibited improved insulin permeability across intestinal epithelial tissue; however, its enteric properties should be improved and clinical effectiveness need to be confirmed by future in vivo studies. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
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A Study of the Mobility of Silver Ions in Chitosan MembranesLin, Elaine Yi-Hua January 2007 (has links)
Chitosan membrane has found applications in biomedical, wastewater treatment, and petrochemical fields that involve the use of silver ions (Ag+). However, mobility of Ag+ in chitosan membranes has seldom been studied. In this study, transport properties of Ag+ in chitosan membranes are studied in-depth, to determine diffusivity coefficient, permeability coefficient, and sorption uptake of Ag+ in chitosan. All parameters are evaluated based on the influence of feed concentration, membrane thickness and operating temperature.
The diffusivity is determined from the time lag obtained from transient diffusion experiments. The permeability is determined from the steady state of permeation experimentally. The diffusivity and corresponding permeability coefficients of Ag+ in chitosan range from to 2.0 10-7 (cm2/s) and from 6.6 10-8 to 2.0 10-7 {mol m/[m2 s (mol/L)]}, respectively, over the conditions tested. Temperature dependencies of these two parameters are found to follow the Arrhenius relationship.
Sorption uptake of the silver salt in chitosan correlates well with the Langmuir isotherm. Also determined from the sorption tests are degree of membrane swelling at different concentrations. This information allows diffusivity coefficients to be determined from the steady state permeation rate. These values of diffusivity are compared with that obtained using the time lag method.
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The effect of pharmaceutical excipients on the release of indomethacin from chitosan beads / Riana HavingaHavinga, Riana January 2006 (has links)
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.
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The effect of pharmaceutical excipients on rifampicin release from chitosan beads / Mangaabane Gorden MohlalaMohlala, Mangaabane Gorden January 2004 (has links)
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.
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Nasal delivery of insulin with Pheroid technology / Tanile de BruynDe Bruyn, Tanile January 2006 (has links)
Approximately 350 million people worldwide suffer from diabetes mellitus (DM) and this
number increases yearly. Since the discovery and clinical application of insulin in 1921,
subcutaneous injections have been the standard treatment for DM. Because insulin is hydrophilic
and has a high molecular weight and low bioavailability, this molecule is poorly absorbed if
administered orally.
The aim of this study is to evaluate nasal delivery systems for insulin, using Sprague Dawley rats
as the nasal absorption model. Pheroid technology and N-trimethyl chitosan chloride (TMC)
with different dosages of insulin (4, 8 and 12 IU/kg bodyweight insulin) was administered in the
left nostril of the rat by using a micropipette. Pheroid technology is a patented (North-West
University) carrier system consisting of a unique oil/water emulsion that actively transports drug
actives through various physiological barriers. These formulations were administered nasally to
rats in a volume of 100 p/kg bodyweight in different types of Pheroids (vesicles, with a size of
1.7 1 - 1.94 pm and microsponges, with a size of 5.7 1 - 8.25 pm).
The systemic absorption of insulin was monitored by measuring arterial blood glucose levels
over a period of 3 hours. The TMC formulation with 4 IU/kg insulin produced clinically relevant
levels of insulin in the blood and as a result also the maximal hypoglycaemic effect. TMC is a
quaternary derivative of chitosan and is able to enhance the absorption of various peptide drugs
by opening tight junctions between epithelial cells. Pheroid formulations were also effective in
lowering blood glucose levels but only at higher doses (8 and 12 IU/kg) of insulin. This study
indicated that Pheroid rnicrosponges had a faster onset of action and a slightly better absorption
of insulin when compared to Pheroid vesicles, but many more studies are needed in this field.
Although the results of this study with absorption enhancers are encouraging, nasal insulin
bioavailability is still very low, and the Pheroid formulations and long-term safety of nasal
insulin therapy have yet to be investigated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.
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Nasal drug delivery of calcitonin with pheroid technology / Jeanéne Celesté KotzéKotzé, Jeanéne Celesté January 2005 (has links)
Advances in biotechnology and recombinant technologies have lead to the
production of several classes of new drugs such as peptide and protein drugs.
These compounds are mostly indicated for chronic use but their inherent
characteristics such as size, polarity and stability prevent them from
incorporation in novel dosage forms. The bioavailability of nearly all peptide
drugs is very low due to poor absorption from the administration site. Several
challenges confront the pharmaceutical scientist in developing effective and
innovative dosage forms for these classes of drugs. A lot of attention has
been given to the nasal route of drug administration for delivery of peptide
drugs. The availability of several promising classes of absorption enhancers
and new drug delivery technologies has also prompt scientists to develop new
delivery systems for nasal administration of peptide drugs.
It has been shown in recent years that N-trimethyl chitosan chloride (TMC), a
quaternary derivative of chitosan, is effective in enhancing the absorption of
several peptide drugs, both in the peroral route and in the nasal route of drug
administration. Early indications are that new drug delivery technologies such
as Pheroid technology will also be able to enhance peptide drug absorption in
the nasal route. The aim of this study was to evaluate and compare the
absorption enhancing abilities of TMC and Pheroid technology in the nasal
delivery of calcitonin, a peptide hormone with low bioavailability.
Pheroid vesicles and Pheroid microsponges were prepared and characterized
for their morphology and size distribution. Calcitonin was entrapped into these
vesicles and microsponges and TMC and TMO solutions (0.5 % w/v),
containing calcitonin, was also prepared. These formulations were
administered nasally to rats in a volume of 100 μl/kg body-weight to obtain a
final concentration of 10 IU/kg body-weight of calcitonin. Plasma calcitonin
and calcium levels were determined over a period of 3 hours.
The results of this study clearly indicated that both Pheroid formulations and
the TMC formulation increase the nasal absorption of calcitonin with a
resulting decrease in plasma calcium levels, indicating an increased
absorption of calcitonin. The highest increase in calcitonin absorption was
obtained with the TMC formulation and this was explained by the difference in
the mechanism of action in enhancing peptide absorption between TMC and
Pheroid technology. It was concluded that Pheroid technology is also a potent
system to enhance peptide drug delivery and that the exact mechanism of
action should be investigated further. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.
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Design and evaluation of chitosan and N-trimethyl chitosan chloride microspheres for intestinal drug delivery / Johannes Petrus VenterVenter, Johannes Petrus January 2005 (has links)
The absorption enhancing ability of chitosan, a linear polysaccharide, is mediated
by protonated amino groups on the C-2 position of the molecules that induce
interaction with the anionic sites on the cell membranes to subsequently alter
tight junction integrity. In neutral and basic environments, such as those found in
the small and large intestines, most chitosan molecules will lose their charge and
precipitate from solution rendering it ineffective as an absorption enhancer. To
increase the solubility of this polymer, methylation of the amino groups on the C-
2 position was proposed.
A partially quaternised and water soluble derivative of chitosan, N-trimethyl
chitosan chloride (TMC), which exhibits superior solubility in a basic environment
compared with other chitosan salts was synthesised and included in a chitosan
microbead solid drug delivery system. Two TMC derivatives were synthesised
by reductive methylation from high and medium molecular weight Chitoclear™
chitosan respectively. The degree of quaternisation calculated from the 1H-NMR
spectra for the medium molecular weight TMC (TMC-M) and the high molecular
weight TMC (TMC-H) polymers were 74.7 % and 48.5 % respectively. The mean
molecular weights of the synthesised TMC-M and TMC-H polymers were 64 100
g/mole and 233 700 g/mole respectively. The effect of different concentrations
TMC-M and TMC-H on chitosan microbeads was studied with results obtained
from scanning electron microscopy (SEM), TMC loading capacity and microbead
swelling behaviour. After selection of the most suitable TMC concentration, the
effect of varying concentration (0.1, 0.2 and 0.5 %) additives on TMC and
ibuprofen release was studied. Commonly used modified cellulose gum (Ac-di-sol®(ADS)), sodium starch glycolate (Explotab®(EXP)) and ascorbic acid (AA)
were added as disintegrants to different microbead formulations to promote
release of both the ibuprofen as model drug and TMC from the beads. It was
noticed that the loading (% drug loading capacity) of TMC-M was much lower
than that obtained with TMC-H while the inclusion of different additives in varying
concentrations did not seem to have a profound influence on the loading of either
TMC-M or TMC-H. It was further noticed from the fit factors (f1 and f2) for
dissolution profiles of eighteen chitosan microbead variations that the formulation
containing TMC-H and 0.5% (w/v) ascorbic acid was the only formulation with a
significantly higher ibuprofen and TMC-H release profile compared to all other
formulations tested.
The chitosan microbead formulation containing 2%(w/v) TMC-H and 0.5 % (w/v)
ascorbic acid (H-AA-0.5) was used for in vitro absorption studies through rat
intestine in Sweetana-Grass diffusion chambers. Chitosan containing TMC-H
(no ascorbic acid) (CHIT-H) only and a plain chitosan microbead (CHIT)
formulation was used as control formulations during the in vitro studies. Although
the H-AA-0.5 formulation exhibited the highest transport rate for ibuprofen, the
mean rate of transport (P app) obtained from the two formulations containing TMCH
(CHIT-H and H-AA-0.5) showed no significant difference in the transport rate of
ibuprofen. Compared to the CHlT formulation as control, both formulations
containing TMC-H exhibited increased ibuprofen transport across in vitro rat
jejunum. However, a statistical significant increase in transport was obtained
only from the H-AA-0.5 formulation in comparison with the CHlT formulation.
It can be concluded that the combination of high molecular weight TMC with a
low degree of quaternisation and ascorbic acid (0.5% w/v) in a chitosan
microbead lead to a statistical significant increase in the in vitro transport rate of
ibuprofen through rat jejunum. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.
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Influence of modified release excipients on ketoprofen release from chitosan particles / W.J. VerweyVerwey, Werner Jaun January 2005 (has links)
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.
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The effect of pharmaceutical excipients on isoniazid release from chitosan beads / Deon van RensburgVan Rensburg, Andries Gideon January 2007 (has links)
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.
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