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UK Journal of Pharmaceutical and Biosciences Vol. 2(1), 1-6, 2014
RESEARCH ARTICLE
UK Journal of Pharmaceutical and Biosciences
Available at www.ukjpb.com
Dissolution behavior of poly vinyl alcohol in water and its effect on the
physical morphologies of PLGA scaffolds
1*
1
1
1
2
Adeyinka Aina , Andrew Morris , Manish Gupta , Nashiru Billa , Neesha Madhvani , Ritika
2
1
2
1
Sharma , Stephen Doughty , Vivek Shah , Yamina Boukari
1
Drug Delivery Laboratory, School of Pharmacy, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor
Darul Ehsan, Malaysia.
2
School of pharmacy, University of Nottingham, University Park, Nottingham, United Kingdom, NG7 2RD.
Article Information
Received 15 January 2014
Received in revised form 19 Feb 2014
Accepted 20 Feb 2014
Keywords:
PVA
Water
Concentration
PLGA
*
Corresponding Author:
E-mail:
[email protected]
Tel.: +60(03)89243422
Abstract
Presented are data from a study of the aqueous properties of Poly Vinyl Alcohol (PVA), a well
studied emulsifying agent, used in the preparation of biodegradeable Poly (DL-Lactide-CoGlycolide) (PLGA) scaffolds/microparticles in water. How these properties affect the physical
morphologies of PLGA scaffolds/microparticles produced from the various PVA solutions at
different concentrations via the water emulsion synthetic method were also evaluated.
UV-Visible absorbance measurements showed a quantitative correlation between the estimated
concentrations of PVA used in solution preparations and the actual concentrations in solution.
The physical appearance/morphologies of the PLGA scaffolds produced from the different PVA
solutions were the same irrespective of the concentration used.
1 Introduction
Poly Vinyl Alcohol (PVA) shown in figure 1 below, is a white
non toxic (included in the FDA inactive database)1,
biodegradeable semi-crystalline polymer. It is produced via
the hydrolysis of poly vinyl acetate under acidic/basic
conditions2.
But more recently, following major advancements in medical and
pharmaceutical research: PVA is now being used in controlreleased
formulations
transdermal patches
9-12
particularly
for
oral-intake4-8
and
in
as well as an emulsifying agent in the
preparation of polylactide and Poly(DL-lactide-co- glycolide)
(PLGA) polymeric nano/micro-particles/scaffolds formulations for
the treatment of age-related diseases of the heart, muscle and
bones13-19.
Made commercially available according to its degree of hydrolysis;
PVA can be classified into two main groups, the partially and full
hydrolysed. The melting point varies depending on the degree of
hydrolysis with the fully hydrolyzed grade having a melting point of
Fig 1: Molecular structure of PVA
First put into commercial use in Germany in the 1920s, PVA has
wide applications in various industries: These include: textiles,
paper, adhesives, cements, and films3.
~228 °C, and the partially hydrolyzed grade ranging from 180-190
°C1.
PVA has been reported to have good aqueous solubility due to its
degree of polarity20 but it also forms dilute polymer solutions that
It is also used as a stabilizing agent for emulsions (0.25–3.0%
does not conform to the ideal-solution behavior21-23. Walker24
weight-per-volume), as a viscosity-enhancers particularly in
explained that this could be due to a relational dependence between
ophthalmic products1. It is used in artificial tears and contact lens
the Cohesive Energy Densities (CED) of both the solute and
solutions for lubrication purposes1.
solvent, while small25 summarized that the solubility of a polymer in
Aina et al. PLGA scaffolds
a non-polymeric liquid depends solely on the heat of mixing. Tacx et
al. 25 suggested that this must be due to ageing of the solutions
leading to the formation of aggregates, a change they thought could
be linked to the thermal history of PVA and the dissolution
temperature.
Duda et al.26-29 and Huggins30 concluded that the molecular diffusion
of a polymer in solution is a complex process, strongly dependent on
temperature, concentration, polymer molecular weight as well as its
morphology, they also reported the presence of an inter-molecular
synergy between the polymer and the solvent molecules at elevated
polymer concentrations which gives rise to a quicker dissolution of
Fig 2: Two dimension representation of the Flory-Huggins
model
the polymer in solution.
○= solvent molecules, ● = solute molecules
These non-ideal behaviour of polymers in solution led Paul Flory31
Due to the limitations of the Flory-Huggings model, a new model
was introduced in 1950, called the Flory-Krigbaum model33-38; which
presented new thermodynamic relationships of dilute solutions in
which individual (heterogeneous) higher molecular weight polymer
chains are isolated and at the same time encircled by regions of
solvent molecules23.
and Maurice Huggins32 to develop a simple lattice model (FloryHuggins model) that could be used to understand this unique
characteristics of polymeric solutions. Based on a set of rules, the
model in its simplest form23 considers the hypothetical mixing of a
low molecular weight solvent1 with a similar molecular weight
solute2. Both solute and solvent molecules are assumed to have
similar size, therefore a single lattice site can only be occupied by
one solute or one solvent molecule at any given time. The increase
Flory and Krigbaum considered the dilute solution as a distribution
of clouds made up of polymer segments enclosed by regions of
pure solvents as compared to the earlier model (Flory-Huggins);
i.e. segmental density was no longer viewed as been uniform23.
in entropy (∆Sm) as a result of the mixing of both solvent and
solute is then obtained using the Boltzmann relationship depicted
While previous authors have compared the dissolution properties
in equation (a) below;
of PVA and other polymers or different molecular weight PVA in
∆Sm = k ln Ω……………… (a)
various solvents, our study aims to look at the dissolution behavior
of PVA in water only; by varying the concentrations of PVA (% w/v)
Given that k is Boltzmann's constant (1.38 x 10-23 J K-1), whereas Ω
added to a fixed volume of water to ascertain; (1) if the actual
gives the total number of ways of arranging n1 identical solvent
concentration of PVA in solution would increase quantitatively as
molecules as well as n2 identical solute molecules, where N = n1 +
the estimated concentration used, (2) how these changes in
n2 is the total number of lattice sites while Ω the probability function
concentration would affect the physical characteristics of PLGA
is estimated as in equation (b) below;
scaffolds produced from the differing PVA solutions.
Ω = N!/(n1!n2!)....... (b)
2 Materials and Methods
While the above generalisation applies only to cases involving low
PVA (fully hydrolyzed) was purchased from Sigma Aldrich, Co 3050
molecular weight solute, the entropy of mixing a higher molecular
spruce street, St. Louis, MO 63103 USA. PLGA was provided by
weight polymer is expected to be lower; this is due to a loss in
Evonik Degussa Corporation, Birmingham, AL 35211 USA. HPLC
conformational entropy brought about by the linkage of individual
grade Dicloromethane (DCM) was obtained from Fischer scientific,
duplicative units along a polymer chain. Thus in expressing the ∆Sm
bishop meadow road, Loughborough, UK, LE11 5RG. Distilled water
for a higher molecular weight polymer in a solvent, the lattice is
was produced for this study using ELGA Purelab flex (Chemopharm,
established by splitting the polymer chain into r number of segments,
47300 Petaling Jaya, Selangor, Malaysia), while Phosphate Buffered
each size of a solvent molecule, where r is the ratio of polymer
Saline (PBS) was supplied by Oxoid limted, Basingstoke, Hamshire,
volume to solvent volume (in a lattice site). So N, the total number of
UK.
lattice sites in this case (for n2 polymer molecules), is re-defined as
2.1 PVA solutions
N = n1 + rn2.
Approximately weighed samples of PVA were added to 250ml of
Figure 2 below; a (lower molecular weight solute versus lower
distilled water pre-heated to 40 °C, under continous stirring. The
molecular weight solvent) and b (higher molecular weight polymer
resulting solution is then stirred and heated (up to 65 °C) without any
(single polymer chain) versus lower molecular weight solvent)
interruption until the PVA is completely dissolved. A total of ten
respectively depicts the lattices in both cases.
samples of varying concentrations (w/v) were prepared; 0.1,
UK J Pharm & Biosci, 2014: 2(1); 2
Aina et al. PLGA scaffolds
0.2......0.9,1.0 % (at higher concentrations PVA aggregation was
amount of solute in solution, absorbance measurements was
observed in solution).
carried out on each of the solutions of PVA used.
2.2 Absorbance measurements
Figure 4 below shows the plot of absorbance against concentration
This was taken using a Biocrim Libra S12 UV-spectrometer
for different PVA concentrations;
(Chemopharm). 276 nm wavelength was used with distilled water
as the reference sample.
2.3 Viscosity measurements
Solution viscosity was measured using the Brookfield viscometer
(DV-I Prime); spindle 62 was deployed at a torque of 75%, with a 3
minutes acquisition time.
2.4 Scaffold preparation
The PLGA microparticles were prepared using the water emulsion
synthetic method. 1 gm of PLGA was weigh and dissolved in 5ml of
DCM, to this was added 250 µl of PBS solution. The resulting mixture
was homogenized (Silverson L5M-A homogenizer; Fischer scientific,
25 Shah Alam, DE 40400, Malaysia) at 9000 rpm for 2 minutes. The
Fig 3: Plot of dissolution time versus concentration
new PLGA/DCM/PBS mixture was then added to 200ml of PVA
solution which was then homogenized at 3000rpm for 2 minutes. The
double emulsion was then stirred for 2 minutes at 300rpm and the
microparticles formed was washed under continuous flow of water in
a sieve (Fischerbrand test sieve number 230) and freeze dried.
2.5 Scanning Electron Microscopy
SEM images were obtained using the Phillip SL 30 (Koninklijke
Philips Electronics N.V.) scanning electron microscope, at a voltage
of 5KV.
3 Results and Discussions
3.1 Dissolution studies
As previously reported21-23, the dissolution of PVA in water over the
Fig 4: Plot of absorbance versus concentration
entire concentration range used in the study was non ideal (in ideal
situation, dissolution time is expected to increase as you have more
It is obvious from the figure 4 above that there is an increase in
solute
absorbance with the increase in concentration, suggesting that the
in
solution;
as
solubility
decreases
with
increased
concentration) as shown in figure 3 below;
amount of PVA in solution increases as the amount weighed to make
up the solutions increases, we were unable to accurately estimate
At low concentrations (0.1 – 0.4), a linear increase in dissolution
(within the limit of reasonable experimental error) the actual
time with concentration was initially observed but after that (at 0.5
concentration in solution due to the non- complete linearity of the plot
and 0.6), a very steep drop was seen, gradually increasing again at
as the molar absorptivity of PVA could not be calculated accurately
0.7 and 0.8 before flattening out at 0.9 and 1.0 % w/v respectively.
from the above calibration plot as defined by the Beer-Lambert's
While we could not adduce this observation to any previous
law40.
theorie(s), a more detail study into this abnormal behavior has
currently been studied to see if such theories can be used to
3.3 Viscosity measurements
understand/explain it and would be published in a separate article.
The results obtained by measuring the liquid viscosities of the PVA
3.2 Absorbance measurements
solutions as a method of monitoring increase in concentration was
inconclusive as previously reported22;
In order to determine if the amount of PVA weighed to make up the
solutions used in the study correlated quantitatively with the actual
UK J Pharm & Biosci, 2014: 2(1); 3
Aina et al. PLGA scaffolds
The specific viscosities for the different solutions were then
Previous authors42 concluded that the relationship between viscosity
calculated using the relationship in equation (c)41;
and concentration reaches a maximum first (in dilute solutions) and
ƞsp = (ƞsolution - ƞsolvent)/ ƞsolvent…
(c)
is then followed by a rapid decrease in viscosity due to the fact that
the polymer (PVA) has reached its final stage of expansion, was not
ƞsp = specific viscosity, ƞsolution = solution viscosity and ƞsolvent =
applicable therefore in this study.
solvent viscosity
3.4 SEM
These were then plotted against concentration as shown in figure 5
below;
Figure 6 below show some SEM images of the PLGA scaffolds
prepared using the PVA solutions used in this study;
The physical appearance/morphologies of the PLGA scaffolds were
the same in all cases regardless of the concentration of PVA used in
the studies; the scaffolds where spherical, porous with rough outer
surfaces.
4 Conclusions
PVA exhibits a non-ideal solution behaviour in water, Nevertheless it
was shown that irrespective of this, its concentration in solution
increases as the amount measured and added to water increases
(within the concentration range used in this study). The physical
morphologies of PLGA scaffolds prepared from the PVA were not
affected by the concentration of PVA in solution.
Fig 5: Plot of concentration against solution viscosity
Fig 6: SEM images of PLGA scaffolds
UK J Pharm & Biosci, 2014: 2(1); 4
Aina et al. PLGA scaffolds
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