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Current Drug Delivery
ISSN: 1567-2018
Current Drug Delivery
Volume 5, Number 1, January 2008
Contents
Preparation & Characterization of Solid Inclusion
Complex of Cefpodoxime Proxetil with β-Cyclodextrin
Pp. 1-6
S. Bhargava and G.P. Agrawal
[Abstract]
Delivery Systems for the Treatment of Proliferative
Vitreoretinopathy: Materials, Devices and Colloidal Carriers
Pp. 7-19
B. Guidetti, J. Azéma, M. Malet-Martino and R.
Martino
[Abstract]
Effect of Sonophoresis and Chemical Enhancers on Testosterone
Transdermal Delivery from Solid Lipid Microparticles: An In
Vitro Study Pp. 20-26
Amal H. El-Kamel, Iman M. Al-Fagih and Ibrahim A. Alsarra
[Abstract]
Stability and Delivery of RNA Via the Gastrointestinal
Tract Pp. 27-31
K.K. Jain
[Abstract]
Formulation and Evaluation of Flurbiprofen Microemulsion
Pp. 32-41
K.W. Ambade, S.L. Jadhav, M.N. Gambhire, S.D. Kurmi, V.J.
Kadam and K.R. Jadhav
[Abstract]
Recent Developments in Taxane Drug Delivery
Pp. 42-54
Ahmad Safavy
[Abstract]
The Clinical Applications of Intranasal Opioids
Pp. 55-58
Katherine Shelley and Michael James Paech
[Abstract]
Orthopedic Implant Used as Drug Delivery System: Clinical
Situation and State of the Research Pp. 59-63
Dominique P. Pioletti, Olivier Gauthier, Vincent A. Stadelmann,
Bruno Bujoli, Jérôme Guicheux, Pierre-Yves Zambelli
and Jean Michel Bouler
[Abstract]
Cyclosporine A Loaded Solid Lipid Nanoparticles: Optimization
of Formulation, Process Variable and Characterization
Pp. 64-69
Jigisha K. Varia, Shamsunder S. Dodiya and Krutika K.
Sawant
[Abstract]
Limonene Enhances the In Vitro and In
Vivo Permeation of Trimetazidine Across a Membrane-Controlled
Transdermal Therapeutic System Pp. 70-76
Yellela S. Krishnaiah and Saleh M. Al-Saidan
[Abstract]
Abstracts
[Back to top]
Preparation & Characterization of Solid Inclusion
Complex of Cefpodoxime Proxetil with β-Cyclodextrin
S. Bhargava and G.P. Agrawal
Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin
antibiotic with poor aqueous solubility and bioavailability.
Effect of β-cyclodextrin
on aqueous solubility and dissolution rate of cefpodoxime
proxetil was evaluated by the formation of solid inclusion
complexes in 1:2 molar ratio of drug: cyclodextrin. Phase
solubility study was carried out whereby a typical B’s
type curve was obtained thus, indicating a 1:2 stoichiometric
ratio for optimum complex formation. Solid inclusion complexes
in 1:2 molar ratios were prepared by using methods such as
physical mixture, solvent evaporation and freeze drying. Prepared
complexes were characterized by fourier transform infrared
spectroscopy (FT-IR) differential scanning calorimetry (DSC),
powder x-ray diffraction (PXRD) and scanning electron microscopy
(SEM). Results of in vitro studies appraised of an
increased solubility and dissolution rate of cefpodoxime proxetil
on complexation with β-
cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst
the complexes prepared by different methods, the complex prepared
by freeze drying showed the highest dissolution rate (P<
0.01). The in vitro antimicrobial activity of cefpodoxime
proxetil and its freeze dried complex (1:2) was studied against
both antibiotic-susceptible and antibiotic-resistant clinical
isolates of Neisseria gonorrhoeae. The freeze dried
complex (1:2) inhibited all penicillin-susceptible strains
and penicillinase-producing strains at 0.015 μg/ml
concentration. Chromosomally resistant strains which were
not responsive to penicillin were inhibited by the complex
at 0.125 μg/ml
concentration. The study revealed that complexation of cefpodoxime
proxetil with β-cyclodextrin
effectively enhanced the aqueous solubility and in vitro
antibacterial activity.
[Back to top]
Delivery Systems for the Treatment of Proliferative Vitreoretinopathy:
Materials, Devices and Colloidal Carriers
B. Guidetti, J. Azéma, M. Malet-Martino and R.
Martino
Proliferative vitreoretinopathy (PVR), the most serious
complication causing retinal detachment surgery to fail, is
one of the leading causes of vision-loss in developed countries.
The pharmaceutical treatment of this disease, located in the
posterior segment of the eye, is problematic because it is
difficult to achieve effective drug levels in the vitreous
and the retina through conventional forms of administration
(topical or systemic). Intravitreal injections can deliver
drugs to the retina without the side-effects associated with
systemic administration. However, because PVR is a long-term
complication and the half-life of most drugs in the vitreous
cavity is short, repeated injections are needed but this can
cause complications. Recent advances in ocular drug delivery
methods and the development of novel bioactive compounds could
lead to new ways for the treatment of PVR. This review will
summarize recent literature concerning intraocular drug delivery
of biopharmaceutical agents for the treatment and prevention
of PVR.
[Back to top]
Effect of Sonophoresis and Chemical Enhancers on Testosterone
Transdermal Delivery from Solid Lipi Microparticles: An
In Vitro Study
Amal H. El-Kamel, Iman M. Al-Fagih and Ibrahim A. Alsarra
The main objective of the study was to investigate the
effect of permeation enhancers and application of low frequency
(LUS) and high frequency ultrasound (HUS) on testosterone
(TS) transdermal permeation after application of testosterone
solid lipid microparticles (SLM). SLM formulations contained
10% compritol and 5 mg TS /g of SLM. The permeation experiments
were performed using Franz diffusion cells and abdomen rat
skin. The examined permeation enhancers were 1% oleic acid
(OA) or 1 % dodecylamine (DA). HUS (1 MHz) was applied in
a continuous mode for 1h at intensity 0.5 W/cm2.
Different intensities and application time of pulsed LUS (20
kHz) were also examined. Additionally, the effect of combination
of US and OA or DA was investigated. Skin irritation and histological
changes were also evaluated.
The results revealed that SLMs have an occlusive effect on
the skin. Statistical analysis revealed the following order
for the permeation of TS: 1% DA for 30 min>HUS +1% DA for
30 min= HUS=HUS + SLM containing 1% OA> SLM containing
1% OA=control. At total application time of LUS 6, 12, and
15 min the flux increased by 1.86, 4.63, and 4.77 fold, respectively.
The enhancement effect of different intensities of LUS was
not directly proportional to the magnitude of intensity. Skin
exposure to HUS or LUS before application of 1% DA for 30
min had no superior enhancement effect over application of
either LUS or HUS alone. Application of drug loaded SLM offered
skin protection against the irritation effect produced by
TS and 1% DA. Histological characteristics of the skin were
affected to various extents by application of enhancers or
ultrasound. In general, application of LUS gave higher TS
permeation than HUS. However, safe application of LUS should
be practiced by careful selection of exposure parameters.
[Back to top]
Stability and Delivery of RNA Via the Gastrointestinal
Tract
K.K. Jain
Oral RNA has been used in the past as a nutritional supplement
as well as a therapeutic agent for several disorders. It is
difficult to validate any of the therapeutic claims in the
absence of scientific studies and in view of the instability
of orally administered RNA. Absorption from the gastrointestinal
tract remains questionable. Most of the current efforts in
relation to oral RNA are devoted to oral administration of
siRNA for therapeutic purposes. A hypothesis is presented
of the usefulness of RNA as a nutraceutical. After review
of the available literature, role of mRNA in the body, and
various routes of administration, suggestions are made for
possible methods to improve delivery of RNA and to study its
pharmacokinetics. There is commercial potential for such a
product if absorption by oral route can be verified as it
is easy to administer and can be produced at lower cost than
intravenous preparations.
[Back to top]
Formulation and Evaluation of Flurbiprofen Microemulsion
K.W. Ambade, S.L. Jadhav, M.N. Gambhire, S.D. Kurmi, V.J.
Kadam and K.R. Jadhav
The purpose of the present study was to investigate the
microemulsion formulations for topical delivery of Flurbiprofen
(FP) in order to by pass its gastrointestinal adverse effects.
The pseudoternary phase diagrams were developed and various
microemulsion formulations were prepared using Isopropyl Myristate
(IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant
and Sorbitan Monooleate as cosurfactant. The transdermal permeability
of flurbiprofen from microemulsions containing IPM and EO
as two different oil phases was analyzed using Keshary-Chien
diffusion cell through excised rat skin. Flurbiprofen showed
higher in vitro permeation from IPM as compared to
that of from EO microemulsion. Thus microemulsion containing
IPM as oil phase were selected for optimization. The optimization
was carried out using 23
factorial design. The optimized formula was then subjected
to in vivo anti-inflammatory study and the performance
of flurbiprofen from optimized formulation was compared with
that of gel cream. Flurbiprofen from optimized microemulsion
formulation was found to be more effective as compared to
gel cream in inhibiting the caragenan induced rat paw edema
at all time intervals. Histopathological investigation of
rat skin revealed the safety of microemulsion formulation
for topical use. Thus the present study indicates that, microemulsion
can be a promising vehicle for the topical delivery of flurbiprofen.
[Back to top]
Recent Developments in Taxane Drug Delivery
Ahmad Safavy
Paclitaxel (taxol, 1a) and docetaxel (taxotere,
1b) have established themselves as an important
class of antitumor drugs cur-rently available to the oncologist.
While the great contribution of these drugs to the management
of the disease and their effect on the improvement of the
patient quality of life could not be overemphasized, a great
deal of research has been ongoing to improve two key pharmacologic
factors, antitumor activity and systemic toxicity. Both physical
and chemical means have been employed towards the enhancement
of antitumor activity and at the same time, lowering the inherent
toxicity and side effects of these drugs. This mini-review
compiles the recent reported works on the design and development
of taxane delivery systems through tumor cell surface receptor-targeted
delivery mechanisms such as small-molecule peptides and monoclonal
antibodies, as well as those on non-targeted procedures such
as liposomes, nanostructures, and natural and synthetic polymers.
[Back to top]
The Clinical Applications of Intranasal Opioids
Katherine Shelley and Michael James Paech
Opioids are widely used in all fields of pain management
and may be delivered by a number of routes of administration.
The intranasal administration of opioid is a convenient route
of transmucosal drug delivery that has received limited attention.
Potential advantages compared with parenteral or oral administration
include avoidance of painful injection, avoidance of risks
associated with intravenous access, rapid onset and titration
to effect, good bioavailability, and high levels of acceptability
and familiarity to patients. These features also lend themselves
to the benefits of patient-controlled delivery systems and
commercially available devices are described.
In this paper we briefly consider the relevant pharmacology
of intranasal drug delivery; opioid drugs and formulations;
and delivery devices used clinically for intranasal administration.
We review the clinical applications of intranasal opioid analgesia.
These have included use for in-hospital pain management in
adult and paediatric populations, in the emergency department,
perioperatively and in burns units. Out-of-hospital use has
included palliative care and paramedic use during retrieval
and transfer to hospital. Many small trials suggest that intranasal
opioids play a useful role in pain management, but large clinical
trials are needed to better define advantages, safety and
acceptability.
[Back to top]
Orthopedic Implant Used as Drug Delivery System: Clinical
Situation and State of the Research
Dominique P. Pioletti, Olivier Gauthier, Vincent A. Stadelmann,
Bruno Bujoli, Jérôme Guicheux, Pierre-Yves Zambelli
and Jean Michel Bouler
A partial review is proposed on the existing literature
for the research performed in orthopedic implant used as drug
delivery system. In the first part, an evaluation is given
on the clinical need to deliver a drug in the surrounding
of an implant. Secondly, a review of the clinical situation
is developed for implants already used as drug delivery system.
Experimental works performed for local delivery are reported.
In particular, a description is given on the in vitro
and in vivo studies where the implant is coated with
different proteins or drugs. Finally, a conclusion is proposed
on the next step in the development of orthopedic implant
as drug delivery system mentioning also the industrial situation.
[Back to top]
Cyclosporine A Loaded Solid Lipid Nanoparticles: Optimization
of Formulation, Process Variable and Characterization
Jigisha K. Varia, Shamsunder S. Dodiya and Krutika K.
Sawant
Solid lipid nanoparticles (SLNs) loaded with Cyclosporine
A using glyceryl monostearate (GMS) and glyceryl palmitostearate
(GPS) as lipid matrices were prepared by melt-homogenization
using high-pressure homogenizer. Various process parameters
such as homogenization pressure, homogenization cycles and
formulation parameters such as ratio of drug: lipid, emulsifier:
lipid and emulsifier: co-emulsifier were optimized using particle
size and entrapment efficiencies as the dependent variables.
The mean particle size of optimized batches of the GMS SLN
and GPS SLN were found to be 131 nm and 158 nm and their entrapment
efficiencies were 83 ±
3.08% and 97 ±
2.59% respectively. To improve the handling processing and
stability of the prepared SLNs, the SLN dispersions were spray
dried and its effect on size and reconstitution parameters
were evaluated. The spray drying of SLNs did not significantly
alter the size of SLNs and they exhibited good redispersibility.
Solid state studies such as Infra Red Spectroscopy and Differential
Scanning Calorimetry indicated absence of any chemical interaction
between Cyclosporine A and the lipids. Scanning Electron Microscopy
of optimized formulations showed spherical shape with smooth
and non porous surface. In vitro release studies
revealed that GMS based SLNs released the drug faster (41.12%
in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of
Cyclosporine A from GMS SLN followed Higuchi equation better
than first order while release from GPS SLN followed first
order better than Higuchi model.
[Back to top]
Limonene Enhances the In Vitro and In Vivo
Permeation of Trimetazidine Across a Membrane-Controlled Transdermal
Therapeutic System
Yellela S. Krishnaiah and Saleh M. Al-Saidan
The objective of the study was to design membrane-controlled
transdermal therapeutic system (TTS) for trimetazidine. The
optimization of (i) concentration of ethanol-water solvent
system, (ii) HPMC concentration of drug reservoir and (iii)
limonene concentration in 2% w/v HPMC gel was done based on
the in vitro permeation of trimetazidine across excised
rat epidermis. A limonene-based membrane-controlled TTS of
trimetazidine was fabricated and evaluated for its in
vivo drug release in rabbit model. The in vitro
permeation of trimetazidine from water, ethanol and selected
concentrations (25, 50 and 75% v/v) of ethanol-water co-solvent
systems showed that 50% v/v of ethanol-water solvent system
provided an optimal transdermal flux of 233.1±3.8 μg/cm2.h.
The flux of the drug decreased to 194.1±7.4
μg/cm2.h
on adding 2% w/v of HPMC to ethanolic (50% v/v ethanol-water)
solution of trimetazidine. However, on adding selected concentrations
of limonene (0, 2, 4, 6 and 8% w/v) to 2% w/v HPMC gel drug
reservoir, the flux of the drug increased to 365.5±7.1
μg/cm2.h.
Based on these results, 2% w/v HPMC gel drug reservoir containing
6% w/v of limonene was chosen as an optimal formulation for
studying the influence of rate-controlling EVA2825 membrane
and adhesive-coated EVA2825 membrane. The flux of the drug
across EVA2825 membrane (mean thickness 31.2 µm) decreased
to 285.8±2.2 μg/cm2.h
indicating that the chosen membrane was effective as rate-controlling
membrane. On applying an adhesive coat (mean thickness 10.2
µm) to EVA2825 membrane, the drug flux further decreased
to 212.4±2.6 µg/cm2.h.
However, the flux of the drug across adhesive-coated EVA2825
membrane-rat epidermis composite was 185.9±2.9 μg/cm2.h,
which is about 2-times higher than the desired flux. The fabricated
limonene-based TTS patch of trimetazidine showed a mean steady
state plasma concentration of 71.5 ng/mL for about 14 h with
minimal fluctuation when tested in rabbits. It was concluded
from the investigation that the limonene-based TTS patch of
trimetazidine provided constant drug delivery across the skin
in rabbit model.
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