Preformulation study of a new dosage form for Parkinson's disease: Orally disintegrating film of ropinirole hydrochloride
14th Central European Symposium on Pharmaceutical Technology (CESPT 2023), Ohrid, Makedonya, 28 - 30 Eylül 2023, cilt.69, ss.111-112, (Tam Metin Bildiri)
- Yayın Türü: Bildiri / Tam Metin Bildiri
- Cilt numarası: 69
- Doi Numarası: 10.33320/maced.pharm.bull.2023.69.03.054
- Basıldığı Şehir: Ohrid
- Basıldığı Ülke: Makedonya
- Sayfa Sayıları: ss.111-112
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
Introduction
Parkinson's disease (PD) is a disease characterized by
a decrease in dopamine levels due to the loss of cells that produce a substance
called dopamine, which allows brain cells to communicate with each other (Simon
et al., 2020).
One of the most crucial dopamine receptor agonists,
ropinirole hydrochloride (ROP), is an active ingredient used not only in PD but
also in restless legs syndrome, which includes symptoms such as burning,
numbness, tremor, tingling, pain, cramping or spasms. ROP is a Class III drug
according to the Biopharmaceutical Classification System (BCS) due to its high
solubility and low permeability.
Orally disintegrating films (ODFs) have attracted a
lot of attention in recent years because it provides an immediate effect after
rapid dissolution, are easy to prepare, and offer ease of use for patients such
as children and the elderly (Patil and Shrivastava, 2014).
The aim of this study is the preparation of new dosage
forms compared to the commercial product containing ROP, which is used in the
treatment of PD and has limitations in use in geriatric patients due to
difficulty in swallowing.
Мaterials
and methods
Firstly, the melting point determination, X-ray powder
diffraction (XRD) analysis, and Fourier-transformed infrared (FTIR) analysis
were performed for the purity analysis of the active substance ROP. The compatibility
study of the formulation components used in the preparation of ROP ODFs was
conducted by FTIR.
Electrospun ODF formulations of ROP were prepared
according to Table 1. ROP ratio was 0.5% (w/w) for all formulations. Polyvinyl
alcohol (PVA) as polymer at different concentration of %10 and %15, propylene
glycol (PG), and polyethyleneglycol 400 (PEG 400) as plasticizers at same
concentration of %10 were used in the formulation. After ODFs are taken on the
tongue, citric acid was used to provide salivary stimulation, sodium lauryl
sulfate as a surfactant, and mannitol to flavor the formulation. Formulation
components were dissolved in distilled water and the nanofibers were obtained
by a flow rate of 1.5 mL/h, collector rotation speed of 200 rpm, nozzle between
collector with a distance of 17 cm, and an applied voltage of 18.5 kV.
Morphological and organoleptic controls of ROP-ODFs
were analyzed by optical microscopy and scanning electron microscopy (SEM).
Disintegration times in distilled water and artificial saliva (with pH 6.75)
were investigated. Also, surface pH measurement was made in ROP ODFs with
Mettler Toledo Seven Compact®.
Results and discussion
Melting point study of pure ROP was made with the
Stuart SMP10 model and it was found to be 251 °C.
Table
1. ROP-ODF formulation parameters
|
PVA ratio |
PG ratio |
PEG 400 ratio |
Citric acid ratio |
SLS ratio |
Mannitol ratio |
|
|
ODF1 |
%10 |
%10 |
- |
%2 |
%1 |
%2 |
|
ODF2 |
%15 |
%10 |
- |
%2 |
%1 |
%2 |
|
ODF3 |
%10 |
- |
%10 |
%2 |
%1 |
%2 |
|
ODF4 |
%15 |
- |
%10 |
%2 |
%1 |
%2 |
Fig.
1. Optical microscopy image of ODF3
In the data of ROP in DrugBank Online, the melting
point is stated between 243 - 250 °C, and the result of the study was found to
be similar to DrugBank.
FTIR and XRD results of ROP were found to be similar
to PubChem and literature (Dudhipala and Gorre, 2020).
The drug-excipient compatibility studies using FTIR
were carried out with physical mixture 1 containing Ropinirole, PVA, PG, citric
acid, SLS, mannitol, and physical mixture 2 containing ropinirole, PVA, PEG
400, citric acid, SLS, mannitol. According to the FTIR result, no
incompatibility was found between the active substance and the excipients.
Morphological and optical evaluations revealed that
ODFs had a flexible and smooth structure. In Figure 1, it is shown that the
fibers are homogeneously and regularly distributed in the optical microscope
image of the ODF3-coded formulation.
The disintegration time of ODFs within 2 cm x 2 cm
dimensions in 10 mL distilled water was measured as 2 s for ODF1, 3 s for ODF2,
3 s for ODF3, and 3 s for ODF4, respectively. Also, the disintegration time of
ODFs within 2 cm x 2 cm dimensions in 10 mL artificial saliva was measured as 3
s for ODF1, 2 s for ODF2, 2 s for ODF3, and 2 s for ODF4, respectively.
The pH measurement results of ODFs were found as 7.075
for ODF1, 7.173 for ODF2, 7.384 for ODF3, and 7.415 for ODF4, respectively.
Conclusion
Preformulation studies for ROP ODF have been carried
out successfully. Rapid disintegration was observed in the mouth with a
disintegration time of 2-3 seconds in all ODF formulation.
All polymer ratios were found to be suitable for the
electrospinning process. Polymer type, polymer ratio, and plasticizer type
directly affected the properties of ROP ODF nanofibers.
Electrospun ODFs could be a potential drug delivery
system for the treatment of PD for ropinirole hydrochloride.
References
Simon,
D.K., Tanner, C.M.,
Brundin, P., 2020.
Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology.
Clinics in Geriatric Medicine.
36 (1), 1-12. https://doi.org/10.1016/j.cger.2019.08.002.
Patil,
P., Shrivastava, S.K., 2014. Fast dissolving oral films: An innovative drug
delivery system. International Journal of Science and Research, 3(7),
2088–2093.
Dudhipala,
N., Gorre, T., 2020. Neuroprotective Effect of Ropinirole Lipid Nanoparticles
Enriched Hydrogel for Parkinson’s Disease: In Vitro, Ex Vivo, Pharmacokinetic
and Pharmacodynamic Evaluation. Pharmaceutics, 12, 448.