Polyvinyl Alcohol-Nanobioceramic Based Drug Delivery
Shameem Shaik1 , Seethalakshmi K2* , Kaviya M1 , Venkatachalapathy B3,Sridhar
1Department of Analytical Chemistry, University of Madras, Guindy Campus, Chennai,
2Department of Chemistry, Rajalakshmi Engineering College, Chennai, India
3Department of Chemistry, SRM Eswari Engineering College, Chennai, India
Seethalakshmi K, Research Scholar, Department of Chemistry, Rajalakshmi
Engineering College, Thandalam, Chennai, India, E-mail: @
Received: September 05, 2016; Accepted: December 12, 2016; Published: June 13, 2017
Shameem Shaik, Seethalakshmi K, Kaviya M, Venkatachalapathy B, Sridhar TM. (2017) Polyvinyl Alcohol-Nanobioceramic Based Drug Delivery System. SOJ Mater Sci Eng 5(1):1-6 DOI: http://dx.doi.org/10.15226/sojmse.2017.00146
Drug delivery research today is an advanced and
important area in pharmaceutical research and application
of nanotechnology includes enhancement of the
solubility and permeability of the drugs so as to improve
their bioavailability including delivery to the targeted
site. Hydroxyapatite (HAP) based bioceramic nanoparticles
composed of biodegradable polymers have been
used in the present work to develop an amoxicillin based
delivery systems. The synthesized n-HAP powders were
estimated for the Ca/p ratio. This ratio indicates the
presence of HAP as a single phase. The nano structure,
morphology and presence of vibrational groups are confirmed
using instrumental analysis. The SEM images
show the spherical shaped particles of nano hydroxyapatite
are confirmed. The loading and unloading characteristics
of the drug were recorded spectro photometrically.
Keywords:Nanofibres; Electrospinning; Polyvinyl Alcohol; Hydroxyapatite;
Various technologies have been explored for different routes
of administration such as oral, parenteral, nasal, dermal, vaginal,
etc. Drug delivery is the method or process of administering a
pharmaceutical compound to achieve a therapeutic effect in humans
or animals. It has been reported that the ultimate therapeutic and toxic effects produced by a drug, when administered
as a solid dosage form and the resultant benefit or risk to a patient,
are dependent on the sum of several interacting variables
associated with the pharmacological properties of the drug, physiological
and pathological factors associated with the patient and
the physicochemical properties of the dosage form [1, 2]. Several
researchers are, therefore, engaged in exploring the physicochemical
aspects of dosage forms and their relationship with therapeutic
efficacy [3, 4]. Different types of drug delivery systems have
been developed by manipulating the physicochemical properties
such as particle size, compound lipophilicity, surface charge, etc.
Several products are available in the market based on these technologies
and a large number of products are in clinical trials but
they are yet to reach the patients. In this context, nanotechnology
has been shown to provide superior drug delivery systems
for a better management and treatment of cancer and other diseases
like AIDS, tuberculosis and malaria. Current efforts in the
area of drug delivery include the development of targeted delivery
in which the drug is only active in the target area of the
body and sustained release formulations in which the drug is released
over a period of time in a controlled manner from a formulation.
The application of nanotechnology in drug delivery
research includes enhancement of the solubility and permeability
of the drugs so as to improve their bioavailability including
delivery to the targeted site like for example malignant tumour.
For the treatment of human diseases, nasal and pulmonary routes
of drug delivery are gaining increasing importance. These routes
provide promising alternatives to parenteral drug delivery particularly
for peptide and protein therapeutics. For this purpose,
several drug delivery systems have been formulated and are being
investigated for nasal and pulmonary delivery. These include
liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins,
among others. biocompatibility, targeting of specific sitesor cell populations in the lung, release of the drug in a predetermined
manner, and degradation within an acceptable period of
time. In order to achieve efficient targeted delivery, the designed
system must avoid the host’s defence mechanisms and circulate to
its intended site of action. Types of sustained release formulations
include liposomes based drug loaded biodegradable microspheres
and drug polymer conjugates.
Nanoparticles (NPs) are defined as particulate dispersions or
solid solutions with a size range of 10-300 nm. Nanoparticle
drugs are designed in such a way that the drug is dissolved, entrapped,
encapsulated or attached to a nanoparticle matrix .
The preparation of nanoparticles depends on the process and the
end product, namely nanospheres, nanocapsules and nanocomposites.
Nanocapsules (NCs) are systems in which the drug is
loaded inside the cavity enclosed by a unique polymer membrane.
Nanospheres are complex matrix systems in which the drug is adsorbed,
dissolved or dispersed throughout the matrix system [6,
7]. Nanocomposites are a multiphase material (usually a mixture
of two or more polymers) where one of the phases has one, two
or three dimensions of nanometer size.
Bioceramics has evolved as an integral and vital segment
of our modern health-care delivery system. The full potential
is yet to be explored in the years to come. Hydroxyapatite
Ca10(PO4)6(OH)2 is a well-established biocompatibile ceramic
capable of forming a strong chemical bond with natural bone.
It is chemically (Ca/P ratio 1.66) and mineralogically identical
with normal human hard tissue- bone and would be stable in
contact with body fluids. In the present work nano hydroxyapatite
(n-HAP) was synthesized and mixed with electrospun PVA
and loaded with amoxillin drug and profile its release.
Materials and Methods
The following reagents and chemicals used in the experiment
were of analytical grade. Calcium nitrate, Cetyl Tri methyl Ammonium
Bromide (CTAB), Ammonium hydrogen phosphate , Ammonia
(for maintaining pH),Ethanol, Amoxicillin trihydrate drug,
Sodium chloride Phosphate buffer. Polyvinyl alcohol, Average
MW equal to 85, 000-124,000 form Sigma Aldrich were used for
Synthesis of nanohydroxyapatite(n-HAP)
Nanohydroxyapatite was prepared by precipitation method.
1M calcium nitrate was prepared and taken in a 500 ml beaker
and maintained the pH -11 by adding ammonia and stirred it for
30 minutes. 0.01mol CTAB was added to the beaker and stirred it
for 1h then 0.67 M of ammonium hydrogen phosphate was added
slowly and maintained pH -10 by adding ammonia with stirring
for 2 hrs, until the precipitate was formed. Aging the precipitate
for 6 h after that wash the filtered precipitate with ethanol and
kept in oven at 800C for 1h. The dried precipitates are crushed into powder form and kept it in the muffle furnace at 8000c for 1
h. The amount of calcium present in the sample was estimated by
complexometric titration using EDTA solution. The color change
from wine red to blue indicates the end point using EBT indicator.
From these values the amount of calcium present was obtained
which was further used to calculate the Ca/P molar ratios.
Electrospinning of PVA
Polymer ceramic nanocomposites were prepared using an
electrospinning apparatus, indigenously designed and developed
apparatus. The PVA incorporated with HAP was prepared by depositing
HAP over nanofibrous membranes. The polymer solutions
were extruded at a speed of 1mL/h by using a syringe pump
(NE-300, New Era Pump Systems, Inc.) with the voltages at 20
KV. Aluminum foil was used as the collector.
For drug loading (Amoxicillin trihydrate), 100 mg of n-HAP
and drug is loaded in a test tube and then add 4ml of 0.15M
NaCl and stir it for 1hr at room temperature. The test tube was
centrifuged at 2000 rpm/min for about 10min. 3ml supernatant
was withdrawn for validation by UV-visible spectrophotometer at
200-400nm. Drug loading can be calculated by
Drug loading (%w/w)= Drug incorporated/Dry powder
weight after loading x100
Amoxicillin loaded n-HAP powder were compressed with electrospun
PVA by a pressure of 25kg/cm2 (2tons) using a hydraulic
press and mini pellets of size, 2mmX2mmX1mm were
prepared. Samples containing 5 mini pellets of each formulation
were placed in a beaker containing 5 ml of pH7.4 phosphate
buffer saline at room temperature [8, 9]. Elution fluids were replaced
by fresh buffer at regular intervals. Removed elution fluids
were collected for determination of drug concentration by UVvisible
spectrophotometer at maximum wavelength at 200-400
The amount of phosphorous content present in the sample as
a phosphomolybdo complex developed with molybdenum blue
method using UV- Spectrophotometry. From the amount of calcium
and phosphorous content present in the sample, the Ca/P
ratios were calculated and found to be 1.67 corresponding to that
of n-HAP. Powder X-ray diffraction (XRD) patterns were obtained
using an X-ray diffractometer equipped (Bruker model D8) using
Cu a radiation (wavelength = λ-1.5406Å) to identify the crystalline
phase, peak positions were compared with standard files.
SEM (Model S-4700, Hitachi) was used to study the morphologies
of the powders. Diffuse Reflectance Spectroscopy (DRS) was
performed on a Shimadzu UV-2450 spectrophotometer. FT-IR was
recorded in ATR mode using UATR Perkin Elmer spectrum II.
Results and Discussion
The synthesized n-HAP powders were estimated for the Ca/P
ratio. The Ca/P ratio of 1.66 corresponding to that of hydroxyapatite
with the formula Ca10(PO4)6(OH)2 was obtained. This ratio indicates the presence of HAP as a single phase. The nano structure, morphology and presence of vibrational groups would
be confirmed using instrumental analysis.
X-Ray Diffraction (XRD)
The XRD patterns n-HAP powder after sintering at 800°C
are shown in the figure 1. n-HAP powder has the corresponding
hkl values (002), (211), (112), (300), (202), (310), (222), (213)
Figure 1: XRD Patterns of nano Hydroxyapatite powder
These hkl values of HAP indexing with JCPDS file no.09-0432
showed a minimal line broadening and sharp intense peak, indicating
a well crystallite material [10-12]. The absence other
calcium phosphate (Tricalcium phosphate) peaks were observed
in the patterns. This confirms the presence of monophasic Hydroxyapatite
in the material.
Figure 2: FTIR spectra of nano Hydroxyapatite powder
FT Infrared Spectroscopy
FT-IR patterns presented in above figure.2, confirm the formation
of n-HAP at different temperatures of 100-800°C. The spectra
possessed an (OH)1 group in the region of 3600 cm-1 and
(PO4-) group comes out from the region of 1100 cm-1. The presence
of phosphate peak is due to P=O stretching and hydroxide peak is due to stretching and bending vibrations. From this analysis
the formation of n-HAP is confirmed .
The successful loading of amoxicillin onto the n-HAP surface
was qualitatively confirmed by FTIR spectroscopy. In the figure.3
the peak at 3570 cm-1 is due to the stretching vibration of amino
and hydroxyl group in amoxicillin structure. The absorption peak
Figure 3: FTIR spectra of nano HAP- amoxicillin powder
at 1070 cm-1 may be due to the stretching vibration of phosphate
group. The FTIR data qualitatively verified the loading of amoxicillin
onto the n-HAP surfaces.
The SEM images of the nano hydroxyapatite indicate the presence
of nano sized grain. The hydroxyapatite nano particles
formed were highly agglomerated and are given in figure 4. The surface of the hydroxyapatite consists of tightly packed grains
forming good adherence. The shaped particles with clumped distributions
are visible from the SEM analysis. The size of the particles
ranges from 50 to 160 nm. The SEM images show the nano
composite after drug loading in the PVA electrospun polymer with
nHAP as given in figure 5. The results reveal that the particles areof random spherical shape with a moderate rough surface indicating
that the drug is homogeneously dispersed with the polymeric
matrix. The SEM image reveals that the nano composites formed
are of narrow size distribution of 200 to 240 nm. The data further
confirms that nano hydroxyapatite has been loaded with amoxicillin
Figure 4: SEM micrographs of Nano hydroxyapatite
The SEM micrographs of Nano hydroxyapatite is presented in
Figure 5: SEM micrographs of Nano hydroxyapatite loaded with
Table 1: Percentage of Drug Loading into the N-HAP and PVA Matrix from UV-Vis Absorption Spectra
Drug loading (%w/w) = Drug incorporated/Dry powder weight after loading ×100
100mg of amoxicillin with n-HAP, PVA
Spectrophotmetic estimation of drug release
The UV spectrum of the PVA, HAP and drug systems is given in
figure. 6-9. figure. 6 and 7 shows the reflection edge wave-
Figure 6: UV visible spectra of amoxicillin drug containing PVA
lengths of PVA and amoxicillin were in the range of 340–400 nm
where as the of n-HAP was smaller than 250 nm. In case of both
n-HAP and amoxicillin and n-HAP, PVA and drug the reflection
in the UV-Vis range was imperfect and a small absorption in this
range is observed. Moreover, it may have had a correlation between
the shift of binding energy and the shift of band gap energy
of the materials. The above results confirmed the loading of the
drug into the n-HAP-PVA matrix.
Figure 7:UV visible spectra of amoxicillin drug containing
n-HAP and PVA
Figure 8:UV visible spectra of amoxicillin drug release in n-HAP
with PVA for22h
The drug loading profiles for n-HAP-PVA with amoxicillin with
respect to loading time have been calculated and the results given
in Table 1. figure. 6-7 shows that the amount of drug is loaded
at 200-400 nm [12, 13]. But, better loading is observed at 277
nm as shown which indicates it is a time independent process.
This confirms that the amount of drug that has been loaded in
the above regions.
Drug release in n-HAP and PVA by mini pellet technique
The release kinetics of amoxicillin/n-HAP/PVA was determined
by recording the absorbance of amoxicillin and PVA at 204 nm
using a UV-visible spectrophotometer. The accumulated release
of amoxicillin was calculated based on a standard amoxicillin absorbance
concentration curve at 204 nm.
The release kinetics of amoxicillin/n-HAP was determined by
Figure 9:UV visible spectra of amoxicillin drug release in n-HAP
with PVA for 48 h
Table 2: Amoxicillin drug release in n-HAP at 22h and 48 h
obtained by UV-visible spectra
Elution of drug
Elution of drug
recording the absorbance of amoxicillin at 202 nm using a UVvisible
spectrophotometer. The accumulated release of amoxicillin
was calculated based on a standard amoxicillin absorbance
concentration curve at 202 nm. The elution studies indicate that
the drug elution occurs at a maximum of 204 nm. Adsorption of
drug amoxicillin on n-HAP and PVA is time independent process.
Drug release has been successfully carried out using minipellet
technique. The release kinetics were carried out between 200-
400 nm. Further studies are needed to understand the percentage
of doses of drug uptake and release with time and changes in
composition n-HAP-PVA matrix.
In conclusion, we have designed and synthesized of nano hydroxyapatite
by precipitation method in pure form. A Ca/P ratio
of 1.67 was confirmed using the crystalline patterns recorded by
XRD and vibrational bands with IR spectrum. SEM analysis indicates
the change in the morphology between n-HAP and n-HAP.
The drug adsorption and release kinetics of n-HAP and amoxicillin
and PVA electrospun fibers were studied by UV analyses.
Validation by UV-visible spectrophotometer was done at a λmax of
208 nm. The elution studies indicate that the drug elution occurs
at a maximum of 204 nm. Adsorption of drug amoxicillin on n-
HAP and PVA is time independent process. The results obtained
indicate that drug loading by n-HAP and PVA is a time dependent
process. The drug release mainly depends on its relation from the
substrate with respective to time. The drug loading techniques
reported are important for tissue engineering and pharmaceutical
The corresponding author express thanks to UGC (Ref.no-
MRP-6089(SERO/UGC)) for the financial assistance supported to
this research work.
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