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International Journal of Pharmaceutical InvestigationNOW IN
Article

Preparation and Evaluation of PLGA-Safinamide Mesylate Nano Particles for the Management of Parkinson’s Disease

Veena Kalyani Sunkanna1★, Vedamurthy Joshi2, Anoop Manjunath3★ Corresponding author

  1. 1Department of Pharmaceutics, Vivekananda College of Pharmacy, Bangalore and Research Scholar, Faculty of Pharmacy, Adichunchanagiri University, B.G. Nagara, Karnataka, INDIA.
  2. 2Department of Pharmaceutics, Faculty of Pharmacy, Adichunchanagiri University, B.G. Nagara, Karnataka, INDIA.
  3. 3Department of Biotechnology, The Oxford College of Engineering, Bommanahalli, Hosur Road, Bangalore, Karnataka, INDIA.

CORRESPONDENCE

Veena Kalyani Sunkanna

Mrs. Veena Kalyani Sunkanna 1Assistant Professor, Department of Pharmaceutics, Vivekananda College of Pharmacy, Bangalore, Research Scholar, Sri Adichunchanagiri College of Pharmacy, B.G. Nagar, Karnataka, INDIA. 2Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, B. G. Nagar, Karnataka, INDIA.

veenakalyani39@gmail.com

Received: 19-01-2026; Revised: 24-03-2026; Accepted: 08-05-2026.

Volume 16, Issue 3 · pp. 1046–1055 · PUBLISHED Jul-Sep 2026 · DOI: 10.5530/ijpi.20260088

View on IJPI original site ↗

ABSTRACT

Aim/Background Parkinson’s Disease (PD) is second most common chronic ongoing neurodegenerative disease recorded in ageing population, which is primarily treated with medications that either replace dopamine or mimic its effects in the brain. In this study, safinamide mesylate popular for its use during “off” episodes in PD was used. PLGA Nanoparticles of Safinamide mesylate (PNS) was prepared and evaluated to improve the bioavailability and targeted delivery of the drug. Materials and Methods PNS prepared by emulsion solvent evaporation method. Various trials were carried out to obtain particles in nano range with optimum drug entrapment. Three different batches of PNS were prepared by varying polymer concentrations. The prepared formulations were evaluated for particle size, zeta potential, drug loading, entrapment efficiency, XRD, TEM etc. and the In vitro release studies of the formulations were recorded. Results Batch PF1(1:1) had particle size of 606 nm, zeta potential of -30 mv, PDI of 0.224, entrapment efficiency of 22.69% and 11.35% of drug loading. Zeta potential was in the range of -24.2 to 30 mV, and zeta potential -30mV of PF1(1:1) ensuring stability. PXRD studies of PF1(1:1) showed amorphous state when scanned at 2θ and coated PNS was clearly identified from TEM images. The results of in vitro drug profiles studies were subjected to curve fitting, where PF1(1:1), followed Korsmeyer-Peppas model and value was 1.963 when compared to other batches. Accelerated studies showed no significant changes in drug content and in vitro release profile. Conclusion Hence it could be predicted that the prepared PNS, due to its inherent nano size will increase permeability of the drug and has the potential to decrease the Tmax and further improve bioavailability in management of Parkinson’s disease.

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INTRODUCTION

Parkinson’s Disease (PD) known as ‘shaking palsy’ is a chronic, degenerative disorder of the brain, associated with motor symptoms and non-motor complications (DeMaagd and Philip, 2015; Jankovic and Tan, 2020). According to the estimation around 9.4 million PD global population in 2020 is higher than the previously reported 6 million PD in 2016 (World Health Organization [WHO], 2020). Parkinson's disease is treated with medications that raise dopamine levels in the brain, influence other chemicals in the brain, and assist manage nonmotor symptoms (Senturk, 2020). One of the popular drugs used in the management of Parkinson’s disease is safinamide mesylate, a Monoamine Oxidase B Inhibitor (MAO-B). It acts centrally, by blocking the oxidation of dopamine in the synapse (Ema, 2016). SAF is approximately 5000 times more selective for MAO-B than MAO-A (1000 times more selective in humans), compared with selegiline (127 times) or (203 times) (Baker and Kim, 2017) rasagiline (Lecht et al., 2007). SAF is a potent drug, which is responsible for a distinct and reversible inhibition of MAO-B with blockade of voltage-dependent NA+ and CA2+ channels and inhibition of glutamate release (National Library of Medicine, 2021). In several controlled release products, poly DL (lactide-coglycolide) 50:50 (PLGA), a copolymer of Poly (Lactic Acid) (PLA) and Poly (Glycolic Acid) (PGA), has been employed as a drug delivery vehicle due to its good biocompatibility and degradability in physiological conditions. A variety of popular solvents, such as tetrahydrofuran, acetone, ethyl acetate, and chlorinated solvents, can dissolve PLGA (Xu and Kim, 2017). Safinamide mesylate (SAF), an inhibitor of monoamine oxidase-B is used as adjunctive therapy, in combination with levodopa and carbidopa (Drug Bank, 2015). SAF, belongs to the BCS class II, whose solubility is highly pH dependent, high solubility at low pH 2 and pH 4, low solubility at pH 6.8 and when orally administered its absolute bioavailability is high (95%) (U.S. Food and Drug Administration, 2017). Thus, in this present work SAF and PLGA was selected. In order to achieve rapid drug absorption, quick onset of action and to improve the bioavailability, we intend to convert this drug into nano (Yetisgin et al., 2020; Ezike et al., 2023; Pratap Singh et al., 2019), delivery systems.

By developing this novel delivery system, we could reduce the dosing demand and avoid gastrointestinal irritation, improve patient compliance and improve the effective delivery of the drug in the treatment of Parkinson’s disease.

MATERIALS AND METHODS

SAF drug, a gift sample from Jubilant Generics, Mysore, PLGA50:50 purchased from Nomisma health care private Ltd., Dichloromethane (DCM) from central drug house Private. Ltd., Polyvinyl Alcohol (PVA) was purchased from Fisher Scientific India Private. Ltd., Mumbai. Distilled water and all other reagents of analytical grade were used with no further purification and dissolution data modelling using DD Solver 1.0 software.

Preparation of PLGA-Nanoparticles of Safinamide mesylate (PNS)

The emulsion solvent evaporation (Alghareeb et al., 2024; Ahadian et al., 2020; Shailender et al., 2017; Operti et al., 2021) technique was used to prepare the nanoparticles (Herdiana et al., 2022). Three different formulations were prepared. The Drug: polymer ratio was 1:1, 1:2 and 1:5. Formulation PF1(1:1) was prepared by mixing the aqueous phase and organic phase. The aqueous phase A containing 0.4%w/v (80 mg) of PVA solution and SAF 25 mg (equivalent to 18.97 mg of safinamide) was mixed thoroughly. The organic phase B contained PLGA (25 mg) dissolved in 10 mL DCM. The organic phase B was added dropwise to the aqueous phase A followed by homogenisation for 30 min and sonicated for 15 min (using PCI Analytics probe sonicator, power 40%, son 30’s, gap 5’s, temp 27ºC) to form oil in water type of emulsion. After sonication, 0.5% w/v (100 mg) PVA solution was added, stirred for 2 hr using magnetic stirrer till organic solvent was evaporated. Then, the emulsion was centrifuged (using Remi centrifuge) at 10,000 rpm for 30 min. The supernatant was separated from the pellet (Figure 1) and the amount of free drug and entrapped drug was carried by measuring the absorbance at 226.5 nm utilizing a UV-visible spectrophotometer (UV-1700 Shimadzu 1700 Japan). The same procedure was followed for all the formulations PF2(1:2), PF3(1:5) prepared by varying the concentration of PLGA and by keeping the drug concentration constant. Formulation (PF0) was without drug (Al-Nemrawi et al., 2018; Chatterjee and Chanda, 2022) shown in Table 1.

Figure 1: Preparation of PNS.
Table 1: Formulations PF0, PF1 (1:1), PF2 (1:2), PF3 (1:5).
Sl. No.ParticularsPF0PF1 (1:1)PF2 (1:2)PF3 (1:5)
1Safinamide mesylate-25 mg25 mg25 mg
2Poly DL (lactide-co- glycolide) 50:5025 mg25 mg50 mg125 mg
3Poly Vinyl Alcohol180 mg180 mg180 mg180 mg
4Dichloromethane10 mL10 mL10 mL10 mL
5Distilled water40 mL40 mL40 mL40 mL

Determination of absorption maxima (λmax) and calibration curve of SAF

Prepared 15 μg/mL solution of SAF in distilled water and scanned in the range of 200 to 350 nm using UV-visible spectrophotometer (UV-1700, Shimadzu, Japan). Calibration curve was prepared by transferring 25 mg of the SAF drug (equivalent to 18.97 mg of safinamide) in 10 mL distilled water. Further dilutions were made then, aliquots 5, 10, 15, 20 and 25 μg/mL solutions (0.5, 1.0, 1.5, 2.0 and 2.5 mL) was prepared using distilled water in 10 mL volumetric flask (EMA/CHMP/393951/2014; Gao et al., 2020) and absorbance was noted using UV-visible spectrophotometer.

Drug and polymer compatibility study by FTIR spectroscopy

The study was carried out by using FTIR Spectrophotometer (Shimadzu IR Spirit) to find out the possible interactions of functional groups between the SAF (Ledesma et al., 2020), polymer PLGA (Gurpreet et al., 2014), physical mixture of SAF with PLGA (Ahmad et al., 2017), and optimized formulation. The samples were compressed into pellets after being finely crushed with IR-grade potassium bromide. Transmissions of infrared spectra were made at room temperature spanning the 4000-500 cm-1 range and its data interpretation was recorded.

Characterization of PNS formulations PF0, PF1 (1:1) PF2 (1:2) and PF3 (1:5)

Utilizing Dynamic Light Scattering (DLS) at 25ºC Zeta sizer nano ZS90 instrument (Malvern Instruments, Malvern, UK) is used to measure the PNS formulations' PF0, PF1(1:1) PF2(1:2) and PF3(1:5) mean Particle Size (PS), Polydispersity Index (PDI), and Zeta Potential (ZP). In clear disposable zeta cells, diluted samples of the PNS in deionized water were placed at 25ºC to evaluate the zeta potentials. Using the Smoluchowski equation, a zeta potential was created using the electrophoretic mobility between the electrodes (Tripathi et al., 2021; Karavelidis et al., 2011) respectively.

Percentage drug Entrapment Efficiency (EE%) and Drug Loading capacity (%DL) of PNS

Drug Loading capacity (%DL) and percentage drug Entrapment Efficiency (EE%) for PNS were calculated. In order to calculate entrapment efficiency, the free quantity of SAF that was not encased inside the NPs was compared to the total amount of SAF used in each formulation of PF1(1:1) PF2(1:2) and PF3(1:5). While formulating PNS, the supernatant that remained over after centrifuging all of the formulations was examined for free SAF using a UV-visible spectrophotometer set to 226.5 nm. The absorbance of this supernatant was then interpolated using a standard calibration curve (Raj et al., 2018; Rukmangathen et al., 2019; Gulati et al., 2014). A total of three measurements was made (n=3).

The drug entrapment efficiency and loading capacity were calculated by using formula given below.

EE% = (total amount of the drug−free drug)/ total amount of the drug x100

%DL = (total amount of the drug-free drug)/ nanoparticles weight x 100

Powder X-ray Diffraction (PXRD)

PXRD is analytical method for characterizing materials, helps in studying the particles in a powdery form in single crystalline material. PXRD (Tabletop XRD Rigaku Mini flex 600 6G) helps to identify the peak positions, intensities, width and shape of the material. Sample PF1(1:1) formulation with 1D scan mode, was scanned within the 3º to 90º with speed of 2.00º per minute with step width of 0.01º respectively. The diffractometer was calibrated with Standard Reference Material 640d. Samples of about 500 mg were used (Pawlak et al., 2021; Lemercier et al., 2023; Nanubolu, 2020) Same procedure was followed for the formulations PF2 (1:2) and PF3 (1:5).

Transmission Electron Microscopy (TEM)

TEM is an analytical technique where an electron beam passes through a sample in which electrons are transmitted or diffracted. Transmitted electrons provide brightfield images which reveal structure with higher contrast. To study morphology of the nanoparticles, sample preparation for TEM analysis (Thermo Fisher Scientific instrument) was carried out.

Sample Preparation for TEM analysis

Approximately 3.5 to 4 μL of sample PF1(1:1) formulation was withdrawn using 10 μL micropipette and placed on the copper coated grid which contained 300 mesh and labelled respectively. Sample PF1(1:1) was fixated on the grid for 10 sec, then the samples were stained first using 3.5 μL uranyl acetate and strained out. Again, the same stain was added to the samples and was rubbed for 5 sec. Allowed the stained sample to dry for 5-8 min. The grid was placed inside the sample cavity, adjusted and closed by tightening the screws in the sample holder. When the instrument indicates the signal (air was replaced by vacuum) then the sample holder was inserted completely. Now the instrument was focussed for general settings and then image on the grid was properly focussed by adjusting the magnification and intensity, once the image focussed was done, the image was captured (Zumaya et al., 2022; Gustafson et al., 2022; Solorzano et al., 2016; Hu et al., 2021). Same procedure was followed for the formulations PF2(1:2) and PF3(1:5).

In vitro release studies

Transferred the sample, 2 mL of formulation PF1(1:1) containing 1.35 mg into a glass tube with lower part of the tube covered with dialysis membrane (cellulose acetate membrane) (Mekjaruskul et al., 2021). The glass tube with dialysis membrane containing sample was placed into 100 mL of aqueous recipient PBS medium (pH 6.8) with continuous stirring at 100 rpm and 37±2ºC, for the complete separation of drug in PBS. At various time intervals (15, 30, 60, 120, 180, 240, 300, 360, 420 and 480 min) the sample was withdrawn and same volume of fresh PBS (pH 6.8) was added and samples were analyzed using UV-visible spectrophotometer (Wolska and Szymanska, 2023; Garg et al., 2014; Weng et al., 2020). Same procedure was followed for formulationsPF2(1:2) and PF3(1:5) and their data were statistically calculated by different models like zero order kinetics (Dash et al., 2010; Laracuente et al., 2020), first order kinetics (Bhattacharyya and Prabhakar, 2015), Higuchi model (Borandeh et al., 2021) and Korsmeyer’s-Peppas model (Jahromi et al., 2020; Sun et al., 2015; Pavaloiu et al., 2021; Jain et al., 2022; Azadi et al., 2017; Jain et al., 2015; Bruschi et al., 2015) study was carried out using DD Solver 1.0 software. All measurements were done in triplicate.

In vitro Statistical release kinetics

Kinetic analysis in drug delivery involves time-dependent experimental evaluations of the release rate of a drug from its formulation. This information is usually acquired from in vitro drug release experiments, where the total amount or percentage of drug released is plotted over time. These data enable the modeling and analysis of release mechanisms and rates through mathematical kinetic models.

Stability study

Stability studies aim to assess and monitor the quality of Active Pharmaceutical Ingredients (API) and Finished Pharmaceutical Products (FPP) affected by various factors including environmental conditions (temperature, humidity, light), interactions between API and excipients, packaging materials, shelf life, or container-closure systems over a specific duration. As per ICH guidelines, the accelerated stability studies were conducted at a temperature of 40ºC±2ºC and 75% RH±5% relative humidity for both the drug and formulations using Temperature and humidity chamber (106 model) (Bajaj et al., 2012). All measurements are done in triplicate.

RESULTS

Drug content estimation

Samples containing pellets and supernatant of all formulations PF1(1:1) PF2(1:2) and PF3(1:5) were analysed for drug content using UV-visible spectrophotometer and the values are 0.527±0.002, 1.651±0.01, 2.109±0.013 mg/mL and 19.325±0.015, 19.51±0.13, 19.95±0.14 mg/mL respectively.

Determination of λmax and calibration curve of SAF using UV-visible spectrophotometer

Prepared SAF (15 μg/mL) solution was scanned by using UV-visible spectrophotometer, and the λmax was found to be 226.5 nm. Then prepared aliquots 5, 10, 15, 20 and 25 μg/mL (0.5, 1.0, 1.5, 2.0 and 2.5 mL) of SAF was analysed at λmax 226.5 nm, absorbance was recorded in Table 2. By plotting concentration versus absorbance, calibration curve of SAF was drawn as depicted in Figure 2.

Figure 2: Graphical representation of calibration curve of SAF using distilled water at 226.5 nm.
Table 2: Calibration curve data of SAF with different concentrations using distilled water.
Concentration (μg/mL)Absorbance*
50.2141±0.009
100.4342±0.0043
150.6237±0.001
200.8204±0.003
250.9994±0.001

Drug and polymer compatibility study using FTIR spectroscopy

The study was carried out to find out the possible interactions of functional groups between the SAF and PLGA and optimized formulation of PF1(1:1).

FTIR spectroscopy study of the SAF, PLGA, SAF-PLGA and optimised PNS PF1(1:1)

SAF shows characteristics absorptions at 3385.38, 2827.81, 1696.97, 1250.62. and 1183.60 cm-1 for the N-H amide, C-H stretching, C=O carbonyl group, ether C-O-C, and C-F stretching modes were observed.

PLGA exhibits molecular vibrations of functional bands at 3500-3450cm-1 which shows stretching vibrations of OH group, 2956.15 with C-H stretching intense bands at 1770 and 1750 cm-1 shows stretching vibration of carbonyl groups. Medium intensity bands between 1300 and 1150 cm-1 are attributed to asymmetric and symmetric-C(=O)-O stretches were observed.

SAF and PLGA showed bands at 3513.7 and 3386.81 with NH-OH molecular bonding, 3197 stretching vibrations of secondary amine N-H, and at 3385 bending vibrations were observed, 2883.42 with C-H stretching 1696-1756.86 and also at 1250 stretching vibrations of C=O, 1390.37 stretching vibrations of S=O, 1182.17 shows stretch of C-F. Results of FTIR spectroscopy of SAF and PLGA showed that they are compatible with each other.

Optimized formulation PF1(1:1) showed that drug-polymer are compatible. No shift in the drug peaks was recorded. The spectra reveal strong OH-NH molecular bonding at bands 3386.81 and 3513.73 depicted in Figure 3.

Figure 3: FTIR Spectra of optimised formulation PF1(1:1).

Characterisation of PNS formulations PF0, PF1(1:1) PF2(1:2) and PF3(1:5)

The mean Particles Size (PS), Polydispersity Index (PDI) and Zeta Potential (ZP) of all formulations PF0, PF1(1:1) PF2(1:2) and PF3(1:5) were analysed using Zetasizer ultra/ advanced instrument and readings of PS are 392.4, 606, 613, 629 nm; PDI are 0.639, 0.224, 0.217, 0.12 (less than 2) and ZP are -4.64, -30, -24.2, -29mV (±30Mv) respectively and optimized PF1(1:1) with PS and ZP as depicted in Figure 4.

Figure 4: Formulation PF1 (1:1) showing a) PS 606.0 and PDI 0.224 b) ZP -30mV.

Percentage drug Entrapment Efficiency (EE%) and loading capacity (%DL) of PNS

Formulations PF1 (1:1) PF2 (1:2) and PF3 (1:5) were analysed for Drug Entrapment Efficiency (EE%) and Drug Loading capacity (%DL) using formula and readings are 22.697±0.01%, 21.953±0.52, 20.186±0.36 and 11.348±0.25, 7.317±0.56 and 3.364±0.65 respectively. All measurements were conducted thrice.

Results of all Formulations PF0, PF1 (1:1) PF2 (1:2) and PF3(1:5) showed that the formulation PF1(1:1) was chosen as optimized formulation when compared to formulations PF2 (1:2) and PF3 (1:5) with respect to PS, PDI, ZP, %EE and %DL.

Powder X-ray diffraction of PNS optimised formulation PF1 (1:1)

The X-ray diffraction pattern of formulation PF1(1:1) which was selected as optimized formulation showed characteristic peak thereby indicating that the amorphous state as shown in Figure 5. Powder X-ray Diffractometry (PXRD) diffraction pattern of SAF was characteristic of an amorphous state with intensity maxima appearing at 4.27º with d A 20.68º and the diffraction pattern obtained for PLGA showed no maximum which confirms its amorphous state indicating that the encapsulation technique used had no effect on the polymer characteristics.

Figure 5: a) PXRD diffraction pattern, b) TEM images from 30 to 700 nm of optimised formulation PF1 (1:1).

Transmission Electron Microscopic (TEM) images of PNS optimised formulations PF1 (1:1)

Selecting formulation PF1(1:1) as optimized formulation, encapsulation of PNS was observed by adjusting magnification of images in TEM (Thermo Fisher Scientific instrument) and the images shown were spherical in shape. This conforms the encapsulation of drug with polymer matrix and images from 30 to 700nm were captured as shown in Figure 5. In vitro studies of PNS formulations PF1 (1:1) PF2 (1:2) and PF3(1:5)

All formulations PF1 (1:1) PF2 (1:2) and PF3(1:5) (each 2 mL) were taken and performed in vitro studies using dialysis membrane and pH 6.8 buffer solutions as medium. Formulations PF1 (1:1) PF2 (1:2) and PF3(1:5) showed drug release kinetics using different drug models like zero order, first order, Higuchi and Korsmeyer-Peppas model and their values with zero order kinetics are 91.86±0.52%, 87.84±0.14%, 61.46±0.80%, with first order kinetics 0.91±0.34, 1.08±0.4, 1.58±0.58, with Higuchi model 91.86±0.52%, 87.84±0.14%, 61.46±0.80% and finally with Korsmeyer-Peppas model 1.96±0.3, 1.94±0.37 and 1.78±0.86 respectively. This significant increase (p<0.05) of SAF release from the formulation could be explained by the drug properties itself. The results explained that PF1 (1:1) followed Korsmeyer-Peppas model as depicted in Figure 6, and statistical kinetics data of all formulations PF1(1:1), PF2 (1:2), PF3 (1:5) their slope (n) was found to be 0.163, 0.213 and 0.068, R2 values were 0.9800, 0.9378 and 0.9537 (Table 3), Akaike Information Criteria (AIC) values are 67.1516, 80.3223 and 69.0446 and Model Selection Criteria (MSC) was found to be 1.8043, 1.0472 and 0.5394 respectively which represented a Fickian type of diffusion of the drug.

Figure 6: Korsmeyer model study of formulation PF1 (1:1), PF2 (1:2), PF3 (1:5).
Table 3: Data on kinetic models with regression values of formulation PF1 (1:1), PF2 (1:2), PF3 (1:5).
FormulationsZero orderFirst orderHiguchiKorsmeyer-Peppas model
k0R2k1R2kHR2kKPnR2
PF1 (1:1)0.2610.71720.0260.82375.2010.860834.5570.1630.98
PF2 (1:2)0.2450.71040.0170.7964.8590.855324.5980.2130.9378
PF3 (1:5)0.1910.47360.0060.80533.9110.666944.2470.0680.9537

Accelerated Stability Study

Stability of nanoparticles is a crucial factor regarding their size and effectiveness. The formulation PF1 (1:1) was placed in securely sealed glass vials and underwent stability testing. The optimized formulation PF1 (1:1) were maintained at room temperature (25ºC±2ºC/60% RH) and under accelerated conditions (40ºC±2ºC/75%±5% RH) and were assessed for drug content and in vitro drug diffusion studies over six months. Results of drug content and in vitro drug release profile over six months at room temperature 25ºC±2ºC/60% RH and accelerated rate are 40ºC±2ºC/75%±5%RH are 90.87%±0.20%, 90.62%±0.21%and 90.67%±0.58%, 90.42%± 0.25% respectively as depicted in Figure 7.

Figure 7: Schematic representation of %drug content and in vitro drug release of PF1(1:1) at room temperature versus accelerated temperature.

DISCUSSION

Three different batches of PNS were prepared by emulsion solvent evaporation method, by varying the ratios of polymer and one batch without drug, Batch PF1 (1:1) had particle size of 606 nm, zeta potential of -30 mV, PDI of 0.224, entrapment efficiency of 22.69% and 11.35% of drug loading. ‘PDI is less than 0.25 hence 99% of the particles are uniform size. Prepared PF1 (1:1) exists in amorphous state when scanned at 2θ using PXRD. TEM images of PF1 (1:1) showed that drug was entrapped by PLGA. Nanoparticles of SAF by emulsion solvent evaporation method with PLGA was successfully developed with particle size in nano range with optimum entrapment. Zeta potential of PNS was in the range of -30 mV ensuring stability. Entrapment efficiency and drug loading were optimum with minimum loss of drug. Invitro drug release models like Zero order, first order, Higuchi and Korsmeyer-Peppas model were applied to the formulations PF1 (1:1) PF2 (1:2) and PF3(1:5). The data indicates that the percentage release of SAF was 91.86±0.52% for PF1 (1:1), 87.84±0.14% for PF2 (1:2), and 61.46±0.80% for PF3(1:5), all measured over an 8-hr period. This notable rise (p<0.05) in SAF release from the formulations may be attributed to the drug's inherent characteristics. SAF, categorized as a BCS class-II drug, exhibits lower solubility in a pH 6.8 buffer solution. Therefore, the enhanced drug release observed from the PF1 (1:1) PF2 (1:2) and PF3(1:5) formulations may result from the drug's incorporation into the nanoparticles, which can readily diffuse through the dialysis membrane in the dissolution medium. A small reduction in the release profile from the PF3(1:5) compared to the PF1 (1:1) and PF2 (1:2) formulations may be attributed to the creation of a PLGA network around the nano drug particles, which served as an obstacle for the drug and consequently slowed its diffusion from the formulation. Upon analyzing the release kinetics data, including zero, first-order, Higuchi, and Korsmeyer- Peppas models, the release profile of SAF from PF1 (1:1) PF2 (1:2) and PF3(1:5) was determined to follow the Korsmeyer-Peppas model, exhibiting the best correlation coefficients (R²) of 0.9800, 0.9378 and 0.9537, correspondingly. This suggests that the release of SAF from the created formulations was not influenced by the drug concentration in the formulation. Upon additional assessment, the kinetics of drug release from the formulations adhere to the Korsmeyer-Peppas model, suggesting that the release is based on diffusion processes from the formulations. To verify the diffusion mechanism from the formulation, the data were additionally analyzed using the Korsmeyer-Peppas equation, where the slope value revealed the release mechanism. Consequently, the drug's release mechanism from the formulations was observed to align with the Korsmeyer-Peppas model, which is due to a mix of diffusion and erosion processes, indicating that this model is the most appropriate, slope value indicated the release mechanism. The slope (n) was determined to be 0.163, 0.213, and 0.068 for the PF1 (1:1) PF2 (1:2) and PF3(1:5) formulations, respectively, indicating a Fickian diffusion type of the drug. The accelerated stability study of optimized formulation PF1 (1:1) was conducted at 25ºC±2ºC/60% RH for drug content, at initial month, 3rd month and 6th month are 91.63±0.1%, 91.28±0.1%, 90.87±0.20% and at 40ºC±2ºC/75% RH showed 91.51±0.06%, 91.18±0.085%, 90.62±0.21% respectively and in vitro drug release at 25±2ºC/60% RH was 91.78±0.035%, 91.16±0.072%, 90.67±0.58% and 40±2ºC/75% RH was 91.53±0.21%, 91.08±0.06%, 90.42±0.25% respectively, hence there was no significant changes in drug content and in vitro drug diffusion studies.

CONCLUSION

PLGA nanoparticles of SAF were prepared by emulsion solvent evaporation method. Three formulations PF1 (1:1) PF2 (1:2), PF3(1:5) (drug with varying concentration) and one formulation PF0(without drug) were developed. Prepared PNS formulations PF1 (1:1) PF2 (1:2), PF3(1:5), choosing PF1 (1:1) with optimum range entrapment using PLGA having particle size 606, polydispersity index 0.224, Zeta potential was in the range of -30 mv ensuring stability. ‘PDI is less than 0.25 hence 99% of the particles are uniform size. Drug Entrapment efficiency was 22.69 and drug loading of 11.35 were optimum with minimum loss of drug. Selected PF1 (1:1) as optimum formulation having maximum drug release when compared to other batches. PXRD revealed that PF1 (1:1) exists in amorphous state, TEM images captured showing encapsulation of SAF with PLGA. In vitro drug profiles of PF1 (1:1) PF2 (1:2) and PF3(1:5), using Korsmeyer Peppas model was 1.963,1.94 and 1.78, R2 values are 0.9800, 0.9378 and 0.9537 respectively. PF1 (1:1) > PF2 (1:2) > PF3 (1:5) followed Korsmeyer Peppas model and considered to be suitable model for this study as it was clearly showed that drug release was not time dependent but it was dependent on diffusion of drug through polymer matrixes. The accelerated stability studies showed no significant changes over 6months in drug content and drug diffusion profile. PNS due to its inherent nano size will increase solubility of the drug and has the potential to decreasing the tmax, cross Blood Brain Barrier (BBB) and further improve bioavailability in treatment of Parkinson’s disease. Thus, taking into account of the PNS results, study was further used for development of intranasal drug delivery system which helps in the management of PD.

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Sunkanna, V. K., Joshi, V., & Manjunath, A. (2026). Preparation and Evaluation of PLGA-Safinamide Mesylate Nano Particles for the Management of Parkinson’s Disease. International Journal of Pharmaceutical Investigation, 16(3), 1046–1055. https://doi.org/10.5530/ijpi.20260088