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Current Drug Delivery
ISSN: 1567-2018
Current Drug Delivery
Volume 4, Number 1, January 2007
Contents
Iontophoresis - An Approach for Controlled Drug
Delivery: A Review Pp. 1-10
Nitin Dixit, Vikas Bali, Sanjula Baboota, Alka Ahuja and
Javed Ali
[Abstract] [Full
Text Article]
PEGylated Dendritic Architecture for Development
of a Prolonged Drug Delivery System for an Antitubercular
Drug Pp. 11-19
P. Vijayaraj Kumar, Hrushikesh Agashe, Tathagata Dutta
and Narendra K. Jain
[Abstract] [Full
Text Article]
Investigation of Enhancement of Solubility of Norfloxacin
β Cyclodextrin
in Presence of Acidic Solubilizing Additives Pp.
21-25
Kamal Dua, M.V. Ramana, U.V. Singh Sara, M. Himaja, Abhinav
Agrawal, Vaibhav Garg and Kavita Pabreja
[Abstract] [Full
Text Article]
Development of Mucoadhesive Patches for Buccal Administration
of Carvedilol Pp. 27-39
Y. Vamshi Vishnu, K. Chandrasekhar, G. Ramesh and Y. Madhusudan
Rao
[Abstract] [Full
Text Article]
Stomach Specific Anti-Helicobacter Pylori Therapy:
Preparation and Evaluation of Amoxicillin-Loaded Chitosan
Mucoadhesive Microspheres Pp. 41-50
Jayvadan K. Patel and Madhabhai M. Patel
[Abstract] [Full
Text Article]
Formulation and Evaluation of Famotidine Floating
Tablets Pp. 51-55
M. Jaimini, A.C. Rana and Y.S. Tanwar
[Abstract] [Full
Text Article]
Hepatitis-B Surface Antigen (HBsAg) Powder Formulation:
Process and Stability Assessment Pp. 57-57
Yuh-Fun Maa, Mahmoud Ameri, Cassandra Shu, Cindy L. Zuleger,
Jenny Che, Jorge E. Osorio, Lendon G. Payne and Dexiang Chen
[Abstract] [Full
Text Article]
Development of Nitrendipine Transdermal Patches: In
vitro and Ex vivo Characterization
Pp. 69-76
Ramesh Gannu, Y. Vamshi Vishnu, V. Kishan and Y. Madhusudan
Rao
[Abstract] [Full
Text Article]
Artificial Organs: A New Option for Treating Osteoarthritis
Pp. 77-88
J. Stöve , L. Lehmann, S. Fickert, T. Aigner and
R. Brenner
[Abstract] [Full
Text Article]
Effects of Lipid Composition and Preparation Conditions
on Physical-Chemical Properties, Technological Parameters
and In vitro Biological Activity of Gemcitabine-Loaded
Liposomes Pp. 89-101
Maria Grazia Calvagno, Christian Celia, Donatella Paolino,
Donato Cosco, Michelangelo Iannone, Francesco Castelli, Patrizia
Doldo and Massimo Fresta
[Abstract] [Full
Text Article]
Abstracts
[Back to top]
Iontophoresis - An Approach for Controlled Drug Delivery:
A Review
Nitin Dixit, Vikas Bali, Sanjula Baboota, Alka
Ahuja and Javed Ali
[Full
Text Article]
The recent approval of lidocaine hydrochloride
and epinephrine combined iontophoretic patch (Lidosite®
Vysteris Inc.) for localized pain treatment by FDA has invigorated
the gaining interest in iontophoretic drug delivery systems
for the transdermal delivery of drugs. This technique of facilitated
movement of ions across a membrane under the influence of
an externally applied electric potential difference, is one
of the most promising physical skin penetration enhancing
method. The rationale behind using this technique is the capability
of this method to increase the systemic delivery of high molecular
weight compounds with controlled input kinetics and minimum
inter-subject variability, which is otherwise achieved only
when parentral route of administration is used. Recently,
good permeation of larger peptides like insulin has been achieved
through this technique in combination with chemical enhancers.
This review briefly describes the factors which affect iontophoretic
drug delivery and summarizes the studies conducted recently
using this technique in order to achieve higher systemic absorption
of the drugs having low passive diffusion otherwise. The effect
of permeation enhancers (chemical enhancers) on iontophoretic
flux of drugs has also been described. Present review also
provides an insight into reverse iontophoresis. Various parameters
which affect the transdermal absorption of drugs through iontophoresis
like drug concentration, polarity of drugs, pH of donor solution,
presence of co-ions, ionic strength, electrode polarity etc.
have also been reviewed in detail.
[Back to top]
PEGylated Dendritic Architecture for
Development of a Prolonged Drug Delivery System for an Antitubercular
Drug
P. Vijayaraj Kumar, Hrushikesh Agashe, Tathagata Dutta
and Narendra K. Jain
[Full
Text Article]
The present study was aimed at developing and exploring
the use of PEGylated poly (propylene imine) dendritic architecture
for the delivery of an anti-tuberculosis drug, rifampicin.
For this study, PEGylated poly(propylene imine) dendritic
architecture was synthesized and loaded with rifampicin. Various
physicochemical and physiological parameters UV, IR, NMR,
TEM, DSC, drug entrapment, drug release and hemolytic toxicity
of both PEGylated and non-PEGylated systems were determined
and compared. The PEGylation of the systems was found to have
increased their drug-loading capacity, reduced their drug
release rate and hemolytic toxicity. The systems were found
suitable for prolonged delivery of rifampicin.
[Back to top]
Investigation of Enhancement of Solubility
of Norfloxacin β
Cyclodextrin in Presence of Acidic Solubilizing Additives
Kamal Dua, M.V. Ramana, U.V. Singh Sara, M. Himaja,
Abhinav Agrawal, Vaibhav Garg and Kavita Pabreja
[Full
Text Article]
The present study is aimed at improving the solubility
of a poorly water-soluble drug, norfloxacin by incorporating
solubilizing additives such as ascorbic acid and citric acid
into the β-cyclodextrin
complexes. Norfloxacin, being amphoteric in nature, exhibits
a higher solubility at pH below 4 and above 8. Addition of
substances like ascorbic acid and citric acid in β-cyclodextrin
complexes reduces the pH of the immediate microenvironment
of the drug below pH 4. In the present work, β-cyclodextrin
complexes of norfloxacin were prepared along with solubilizing
additives such as citric acid and ascorbic acid in various
proportion and the dissolution profile was performed in both
HCl buffer, pH 1.2 and phosphate buffer, pH 7.4. The results
have shown an enhanced dissolution rate in both media. DSC
and IR spectral studies performed on the solid complexes have
shown that there is no interaction of the drug with the additives
and β-cyclodextrin.
Disc diffusion studies have shown larger diameters of zone
of inhibition indicating a greater diffusivity of the drug
into the agar medium.
[Back to top]
Development of Mucoadhesive Patches for
Buccal Administration of Carvedilol
Y. Vamshi Vishnu, K. Chandrasekhar, G. Ramesh
and Y. Madhusudan Rao
[Full
Text Article]
A buccal patch for systemic administration of carvedilol
in the oral cavity has been developed using two different
mucoadhesive polymers. The formulations were tested for in
vitro drug permeation studies, buccal absorption test,
in vitro release studies, moisture absorption studies
and in vitro bioadhesion studies. The physicochemical
interactions between carvedilol and polymers were investigated
by Fourier transform infrared (FTIR) Spectroscopy. According
to FTIR the drug did not show any evidence of an interaction
with the polymers used and was present in an unchanged state.
XRD studies reveal that the drug is in crystalline state in
the polymer matrix. The results indicate that suitable bioadhesive
buccal patches with desired permeability could be prepared.
Bioavailability studies in healthy pigs reveal that carvedilol
has got good buccal absorption. The bioavailability of carvedilol
from buccal patches has increased 2.29 folds when compared
to that of oral solution. The formulation AC5 (HPMC E 15)
shows 84.85 ±
0.089% release and 38.69 ±
6.61% permeated through porcine buccal membrane in 4 hr. The
basic pharmacokinetic parameters like the Cmax,
Tmax and AUCtotal were calculated and
showed statistically significant difference (P<0.05) when
given by buccal route compared to that of oral solution.
[Back to top]
Stomach Specific Anti-Helicobacter Pylori
Therapy: Preparation and Evaluation of Amoxicillin-Loaded
Chitosan Mucoadhesive Microspheres
Jayvadan K. Patel and Madhabhai M. Patel
[Full
Text Article]
The purpose of this research was to formulate and
systematically evaluate in vitro and in vivo
performances of mucoadhesive amoxicillin microspheres for
the potential use of treating gastric and duodenal ulcers,
which were associated with Helicobacter pylori.
Amoxicillin mucoadhesive microspheres containing chitosan
as mucoadhesive polymer were prepared by simple emulsification
phase separation technique using glutaraldehyde as a cross-linking
agent. Results of preliminary trials indicate that volume
of cross-linking agent, time for cross-linking, polymer-to-drug
ratio, and speed of rotation affected characteristics of microspheres.
Microspheres were discrete, spherical, free flowing and also
showed high percentage drug entrapment efficiency. In
vitro mucoadhesive test showed that amoxicillin mucoadhesive
microspheres adhered more strongly to gastric mucous layer
and could retain in gastrointestinal tract for an extended
period of time. A 32 full factorial design was employed to
study the effect of independent variables, polymer-to-drug
ratio (X1), and stirring speed (X2) on dependent variables
i.e. percentage mucoadhesion, t80, drug entrapment efficiency,
particle size and swelling index. The best batch exhibited
a high drug entrapment efficiency of 70 % and a swelling index
of 1.39; percentage mucoadhesion after 1 h was 79 %. The drug
release was also sustained for more than 12 h. The polymer-to-drug
ratio had a more significant effect on the dependent variables.
The morphological characteristics of the mucoadhesive microspheres
were studied using scanning electron microscopy. In vitro
release test showed that amoxicillin released slightly faster
in pH 1.0 hydrochloric acid than in pH 7.8 phosphate buffer.
In vivo H. pylori clearance tests were also
carried out by administering amoxicillin mucoadhesive microspheres
and powder, to H. pylori infectious Wistar rats under
fed conditions at single dose or multiple dose(s) in oral
administration. The results showed that amoxicillin mucoadhesive
microspheres had a better clearance effect than amoxicillin
powder. In conclusion, the prolonged gastrointestinal residence
time and enhanced amoxicillin stability resulting from the
mucoadhesive microspheres of amoxicillin might make contribution
complete eradication of H. pylori.
[Back to top]
Formulation and Evaluation of Famotidine
Floating Tablets
M. Jaimini, A.C. Rana and Y.S. Tanwar
[Full
Text Article]
The purpose of this investigation was to prepare
a gastroretentive drug delivery system of famotidine. Floating
tablets of famotidine were prepared employing two different
grades of methocel K100 and methocel K15M by effervescent
technique; these grades of methocel were evaluated for their
gel forming properties. Sodium bicarbonate was incorporated
as a gas-generating agent. The floating tablets were evaluated
for uniformity of weight, hardness, friability, drug content,
in vitro buoyancy and dissolution studies. The effect
of citric acid on drug release profile and floating properties
was investigated. The prepared tablets exhibited satisfactory
physico-chemical characteristics. All the prepared batches
showed good in vitro buoyancy. The tablet swelled
radially and axially during in vitro buoyancy studies.
It was observed that the tablet remained buoyant for 6-10
hours. Decrease in the citric acid level increased the floating
lag time but tablets floated for longer duration. A combination
of sodium bicarbonate (130mg) and citric acid (10mg) was found
to achieve optimum in vitro buoyancy. The tablets
with methocel K100 were found to float for longer duration
as compared with formulations containing methocel K15M. The
drug release from the tablets was sufficiently sustained and
non-Fickian transport of the drug from tablets was confirmed.
[Back to top]
Hepatitis-B Surface Antigen (HBsAg) Powder
Formulation: Process and Stability Assessment
Yuh-Fun Maa, Mahmoud Ameri, Cassandra Shu, Cindy
L. Zuleger, Jenny Che, Jorge E. Osorio, Lendon G. Payne and
Dexiang Chen
[Full
Text Article]
The purpose of this study was to develop a hepatitis-B
surface antigen (HBsAg) dry powder vaccine formulation suitable
for epidermal powder immunization (EPI) via an efficient,
scalable powder-formation process. Several HBsAg dry powder
formulations were prepared using four different powder-formation
methods: freeze-drying/compress/grind/sieve (FD/C/G/S), spray-drying
(SD), agarose beads, and spray freeze-drying (SFD). Powder
properties and physical stability were determined using particle
size analysis, tap density measurement, scanning electron
microscopy, optical microscopy, and moisture content analysis.
Physical, chemical and biochemical stability of HBsAg was
determined by dynamic light scattering, an enzyme immune assay,
and immunogenicity in a mouse or hairless guinea pig model.
Out of the four powder-formation methods evaluated SFD outperformed
other methods in the following considerations: good process
efficiency, flexible scalability, and desirable particle characteristics
for skin penetration. The stress posed by SFD appeared to
be mild as HBsAg in the dry form retained its potency and
immunogenicity. Notably, the mechanism of fast freezing by
SFD actually promoted the preservation of HBsAg nanoparticle
size, in good correlation with long-term biochemical stability.
Among several formulations screened, the formulation containing
10 μg
HBsAg in 1-mg powder with a tertiary mixture of trehalose,
mannitol, and dextran, exhibited excellent overall stability
performance. In conclusion, HBsAg dry powder formulations
suitable for EPI were successfully prepared using SFD. Further,
a systematic formulation development strategy allowed the
development and optimization of an HBsAg dry powder formulation,
demonstrating excellent long-term physical, biochemical, and
immunological stability.
[Back to top]
Development of Nitrendipine Transdermal
Patches: In vitro and Ex vivo Characterization
Ramesh Gannu, Y. Vamshi Vishnu, V. Kishan and
Y. Madhusudan Rao
[Full
Text Article]
OBJECTIVE: The aim of the investigation
was to develop and evaluate matrix type transdermal drug delivery
systems (TDDS) of nitrendipine (NTDP).
EXPERIMENTAL: The matrix type TDDS of NTDP
were prepared by solvent evaporation technique. Ten formulations
(composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose
in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4 in formulations A1,
A2, A3, A4, A5 and Eudragit RS 100 and Hydroxypropyl methyl
cellulose in the same ratios in formulation B1, B2, B3, B4,
B5 respectively) were prepared. All formulations carried 6
% v/w of carvone as penetration enhancer and 15% v/w of propylene
glycol as plasticizer in dichloromethane and methanol as solvent
system. The prepared TDDS were evaluated for in vitro
release, ex vivo permeation, moisture absorption,
moisture content and mechanical properties. The physicochemical
interactions between nitrendipine and polymers were investigated
by Fourier Transform Infrared (FTIR) Spectroscopy.
RESULTS: The maximum drug release in 24 hrs
for A series formulations was 89.29% (A4) and 86.17% for B
series (B5), which are significantly (p < 0.01) different
to the lowest values (57.58 for A1 and 50.64 for B1). Again
formulations A4 (flux 23.51 μg/hr/cm2)
and B5 (flux 22.98 μg/hr/cm2)
showed maximum skin permeation in the respective series. The
flux obtained with formulation A4 and B5 meets the required
flux (19.10 μg/hr/cm2).
The mechanical properties, tensile strength, elastic modulus
(3.42 kg/mm2 for A4 and 4.25 kg/mm2
for B5) reveal that the formulations were found to be strong
but not brittle. FTIR studies did not show any evidence of
interaction between the drug and the polymers.
CONCLUSION: Nitrendipine matrix type transdermal
therapeutic systems could be prepared with the required flux
having suitable mechanical properties.
[Back to top]
Artificial Organs: A New Option for Treating
Osteoarthritis
J. Stöve , L. Lehmann, S. Fickert, T. Aigner and
R. Brenner
[Full
Text Article]
Osteoarthritis is usually regarded as a localized
disease whose optimal treatment is a therapy applied directly
to the affected joint. Unfortunately, current local therapies
such as repeated intraarticular injections or constant infusions
are associated with a higher risk of infection. One way to
overcome this would be to transfer substances made locally
by cells within the joint. However, attempts using direct
vector transfers or intraarticular injections of ex vivo modified
cells could not achieve a sustained protein secretion over
several months. Another method of delivering biological factors
(i.e.growth hormones) intraarticularly is to transplant an
artificial organ, capable of supporting the regeneration of
natural cartilage, directly into the affected joint The main
difficulty of having to produce bioactive factors over a long
period of time is overcome by implanting a chamber-like system
filled with either genetically modified cells or a drug-releasing
matrix. This drug delivery system would be located at a peripheral
site of the joint and could release substances directly into
the joint cavity which would be transported via the
synovial fluid and/or diffused to the chondrocytes or synoviocytes.
[Back to top]
Effects of Lipid Composition and Preparation
Conditions on Physical-Chemical Properties, Technological
Parameters and In vitro Biological Activity of Gemcitabine-Loaded
Liposomes
Maria Grazia Calvagno, Christian Celia, Donatella Paolino,
Donato Cosco, Michelangelo Iannone, Francesco Castelli, Patrizia
Doldo and Massimo Fresta
[Full
Text Article]
The effects of lipid composition and preparation
conditions on the physicochemical and technological properties
of gemcitabine-loaded liposomes, as well as the in vitro
anti-tumoral activity of various liposome formulations were
investigated. Three liposome formulations were investigated:
DPPC/Chol/Oleic acid (8:3:1 molar ratio, liposomes A), DPPC/Chol/DPPS
(6:3:1 molar ratio, liposomes B) and DPPC/Chol/DSPE-MPEG (6:3:1
molar ratio, liposomes C). Multilamellar liposomes were prepared
by using the TLE, FAT and DRV methods, while small unilamellar
liposomes were obtained by extrusion through polycarbonate
filters. Light scattering techniques were used to characterize
liposome formulations. Loading capacity and release profiles
of gemcitabine from various liposome formulations were also
investigated. Caco-2 cells were used to evaluate in vitro
the antitumoral activity of gemcitabine-loaded liposomes with
respect to the free drug and also the intracellular drug uptake.
Preparation methods and liposome lipid composition influenced
both physicochemical parameters and drug delivery features.
Liposomes with a size ranging from 200 nm to 7 µm were
obtained. The gemcitabine entrapment was higher than that
expected probably due to an interaction with the liposome
lipid components. The following decreasing loading capacity
order was observed: liposome B>liposome C>liposome A.
Gem-citabine release from various liposome formulations is
modulated by two different processes, i.e. desorption from
and permeation through liposomal bilayers. MTT assay showed
a greater cytotoxic effect of gemcitabine-loaded liposomes
with respect to the free drug. The following decreasing anticancer
activity order was observed between the various liposome formulations:
liposome C>liposome A>liposome B. The increased anticancer
activity is correlated to the ability of the colloidal carrier
to increase the intracellular drug uptake. Due to the encouraging
results and to the high liposome modularity various applications
of potential therapeutic relevance can be envisaged for liposomes.
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