Development And Evaluation of Fast Dissolving Oral Films of Selegiline and Lazabemide for Enhanced Neuroprotection

Gattu Venkata Sravani, Dr. Mungi Rama Krishna,

doi:10.5281/zenodo.17422087

Research Paper | Open Access
Volume 03 | Issue 10 | Article Id IJPS/250310353

Development And Evaluation of Fast Dissolving Oral Films of Selegiline and Lazabemide for Enhanced Neuroprotection
Gattu Venkata Sravani* Dr. Mungi Rama Krishna
Avanthi Institute of Pharmaceutical Sciences, Hyderabad.

Abstract

The present research focused on the formulation and evaluation of fast-dissolving oral films of Lazabemide and Selegiline to enhance therapeutic outcomes in Parkinson’s disease. Hydroxypropyl methylcellulose (HPMC) of varying grades was employed as the main film-forming polymer, while plasticizers were incorporated to improve flexibility and handling. Optimization involved adjusting polymer concentrations and using suitable superdisintegrants to ensure rapid disintegration along with adequate mechanical properties. The prepared films were characterized for physicochemical and mechanical parameters, including thickness, uniformity of weight, tensile strength, percent elongation, folding endurance, surface pH, and drug content. In-vitro disintegration and dissolution studies confirmed fast release of the active drugs, with formulations F16 (Lazabemide) and F18 (Selegiline) showing superior performance. FTIR spectra demonstrated the absence of drug–excipient interactions, while SEM confirmed uniform drug distribution in the amorphous state. The optimized films also exhibited stability under accelerated conditions. These findings highlight that HPMC-based fast-dissolving films are a promising alternative dosage form, offering rapid onset of action, improved bioavailability, and better patient compliance in Parkinson’s therapy.

Keywords

Lazabemide, Selegiline, Fast-dissolving oral films, HPMC, Parkinson’s disease

Introduction

Fast dissolving oral films (FDOFs) represent an innovative delivery platform that rapidly disintegrates in the mouth without water, enhancing patient compliance—especially among those with swallowing difficulties—and enabling rapid absorption that bypasses first-pass metabolism. Selegiline (a selective irreversible MAO-B inhibitor) and lazabemide (a reversible MAO-B inhibitor) both offer neuroprotective benefits in Parkinson’s disease but are limited by low oral bioavailability, rapid metabolism, and dosing challenges. Transforming them into fast dissolving oral films offers several advantages: improved bioavailability, reduced gastrointestinal degradation, and patient-friendly administration. Previous studies have demonstrated the feasibility of formulating selegiline as mouth-dissolving films to bypass first-pass loss and enhance therapeutic onset. Fast dissolving film technology has been widely adopted for delivering poorly soluble or rapidly metabolized drugs, leveraging various polymers for optimal film formation, disintegration, and drug release. This study aims to develop, characterize, and validate fast dissolving oral films containing selegiline and lazabemide for enhanced neuroprotective delivery. Parameters such as mechanical strength, film uniformity, disintegration time, drug release profile, and stability under ICH conditions are evaluated, following ICH Q2(R1) analytical validation guidelines.

MATERIALS AND METHODS

Lazabemide

Lazabemide was obtained as a crystalline, odorless, and water-soluble solid. The melting behavior and solubility confirmed its identity and purity. The molecular weight (218.25 g/mol) and formula (C??H??N?O?) were in accordance with literature. UV standardization in pH 6.8 buffer produced a linear calibration curve with correlation coefficient above 0.999, indicating excellent linearity. The drug demonstrated rapid dissolution, though its oxidative instability suggested the necessity of protective formulation approaches.

Selegiline

Selegiline appeared as a white crystalline solid with molecular weight 187.28 g/mol (C??H??N). Calibration curve in phosphate buffer showed linearity (R² > 0.998). The drug exhibited extensive first-pass metabolism and short half-life, consistent with pharmacokinetic reports. The experimental data confirmed that controlled or fast-dissolving film strategies are required to maintain systemic levels.

Excipients

All excipients used (HPMC, maltodextrin, xanthan gum, propylene glycol, citric acid, aspartame, and flavors) complied with pharmacopeial standards. Their organoleptic and functional properties supported film formation, taste masking, and stability. HPMC polymers were confirmed as suitable film-formers, while PEG 400 and propylene glycol enhanced flexibility. Sweeteners and flavors improved palatability, and no incompatibility was observed during preliminary mixing.

RESULTS AND DISCUSSION

UV Spectral Analysis

Lazabemide showed λmax at 265 nm with a linear calibration curve (10–50 µg/mL) and R² > 0.999, confirming Beer–Lambert compliance. Selegiline exhibited λmax at 220 nm with linearity across 5–40 µg/mL and R² > 0.998, ensuring suitability for analysis.

Formulation Development

Fast-dissolving films of Lazabemide and Selegiline were successfully prepared by solvent casting. The polymer and plasticizer ratios were optimized across eighteen trials for each drug. Films were smooth, uniform, and non-sticky, with thickness between 120–180 µm, within acceptable pharmacopeial limits. Weight variation was minimal (<5%), surface pH ranged 6.5–6.9 (neutral and non-irritant), and drug content uniformity exceeded 98% for all formulations.

Table 1: Formulation Trials of Lazabemide Films (F1–F18)

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12	F13	F14	F15	F16	F17	F18
Lazabemide (mg)	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89	15.89
HPMC 5CPS (mg)	80	90	100	110	120	130	100	110	120	130	140	150	-	-	-	-	-	-
HPMC 15CPS (mg)	100	110	120	100	110	120	-	-	-	-	-	-	110	120	130	130	120	110
HPMC 50CPS (mg)	-	-	-	-	-	-	100	120	140	160	180	200	120	130	140	150	140	130
PEG 400 (mg)	100	110	120	100	110	120	100	110	120	130	140	150	100	110	120	130	140	150
Crospovidone (mg)	5	5	5	-	-	-	6	7	8	-	-	-	-	12	-	14	-	10
SSG (mg)	-	-	-	5	5	5	-	-	-	6	7	8	10	-	11	-	12	-
Citric Acid (mg)	40	40	40	40	40	40	40	40	40	40	40	40	40	40	40	40	40	40
Aspartame (mg)	8	8	8	8	8	8	8	8	8	8	8	8	8	8	8	8	8	8
Flavor (Strawberry)	QS
Distilled Water	QS

Table 2: Formulation Trials of Selegiline Films (F1–F18)

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12	F13	F14	F15	F16	F17	F18
Selegiline (mg)	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47	79.47
HPMC 5LV (mg)	80	80	80	100	100	100	-	-	-	-	-	-	-	-	-	-	-	-
HPMC 15LV (mg)	100	110	120	130	140	150	80	80	80	100	100	100	80	80	80	100	100	100
HPMC 50LV (mg)	-	-	-	-	-	-	120	140	160	180	200	220	-	-	-	-	-	-
HPMC K4M (mg)	-	-	-	-	-	-	-	-	-	-	-	-	240	260	280	300	320	340
Crospovidone (mg)	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18
Propylene Glycol (mg)	100	100	100	110	110	110	120	120	120	130	130	130	140	140	140	150	150	150
Citric Acid (mg)	50	50	50	50	50	50	50	50	50	50	50	50	50	50	50	50	50	50
Sucrose (mg)	10	10	10	10	10	10	10	10	10	10	10	10	10	10	10	10	10	10
Menthol	QS
Vanillin	QS
Water	QS

Evaluation

Physical Characterization

The prepared Lazabemide and Selegiline films were evaluated for their physical parameters, and all values were found within acceptable pharmacopeial limits. Lazabemide films (F1–F18) showed consistent weight (21–28 mg), uniform thickness (0.23–0.28 mm), and rapid disintegration ranging from 9–22 seconds. Drug content was between 90–99%, with folding endurance exceeding 90 folds, confirming good flexibility and strength. Surface pH remained close to neutral (6.2–6.8), minimizing risk of mucosal irritation. Similarly, Selegiline films exhibited uniform weight (23–28 mg), thickness (0.24–0.26 mm), and disintegration within 9–19 seconds. Drug content ranged from 88–99%, and folding endurance values above 95 folds indicated mechanical stability. Moisture content was low (3–4%), suggesting good storage stability. Tensile strength and elongation studies of optimized formulations (F16 for Lazabemide and F18 for Selegiline) showed adequate film strength (11.4–12.1 g/cm²) with elongation between 9–10%, ensuring flexibility without brittleness. Overall, the physical evaluation confirmed that the formulated fast dissolving films were mechanically stable, pharmaceutically acceptable, and suitable for oral administration.

In vitro disintegration studies

All formulations of Lazabemide disintegrated within 8–21 seconds, with the optimized film F16 showing the fastest disintegration of 8 seconds, confirming its suitability for rapid therapeutic onset. Similarly, Selegiline films disintegrated within 8–19 seconds, with F18 exhibiting the shortest disintegration time of 8 seconds, ensuring early drug availability.

In-vitro drug dissolution

In-vitro dissolution studies (Tables 14–16, Figures 23–25) demonstrated rapid drug release for both drugs. Lazabemide formulations showed maximum release of 99.39 ± 5.28% for the optimized batch F16 within 9 minutes, indicating superior solubility and fast release characteristics. Selegiline films also exhibited efficient release, with F18 reaching near-complete release of above 95% within 9 minutes, confirming its potential for enhanced bioavailability.

Table 3: In vitro drug release -F1 to F18- Lazabemide

Time (min)	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12	F13	F14	F15	F16	F17	F18	MP
0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
1	31	43	23	33	28	30	50	29	50	45	34	38	55	50	45	64	49	39	26
3	52	60	39	49	37	49	72	35	66	72	47	49	67	65	56	76	54	50	34
5	63	73	46	55	45	56	81	42	72	83	54	58	74	80	64	83	68	64	48
7	75	85	60	64	64	75	91	56	82	90	69	66	83	85	76	90	72	79	54
9	82	96	69	72	83	85	96	74	95	96	79	72	93	92	89	99	81	94	79
10	92	96	90	90	93	96	90				89	90	96		91		90		92

Table 4: In vitro drug release - F1 to F18- Selegiline

Time (min)	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12	F13	F14	F15	F16	F17	F18	MP
0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
1	33	40	49	35	50	39	48	37	41	54	56	33	30	34	49	54	58	65	28
3	48	60	52	48	62	45	54	56	59	68	60	48	46	54	67	62	65	82	36
5	56	73	65	69	72	59	68	65	69	72	71	55	58	78	77	74	79	90	49
7	70	82	71	76	88	64	81	74	83	85	83	62	70	84	83	86	82	100	68
9	81	93	88	80	94	72	95	83	96	90	92	80	85	92	90	93	89		72
10	95		96	94		89		97				94	90		92		95		85

Values are expressed in mean± SD (n=3)

Overall, disintegration and dissolution studies revealed that both optimized formulations (F16 for Lazabemide and F18 for Selegiline) fulfilled the requirements of fast-dissolving films by providing rapid disintegration, quick drug release, and early onset of action, making them promising candidates for improved neuroprotective therapy.

Table5: Optimized Formulation Details of Lazabemide and Selegiline

Parameter	F16 (Lazabemide)	F18 (Selegiline)
Thickness (mm)	0.23	0.24
Weight (mg)	21	22
Folding Endurance	120	115
Surface pH	6.5	6.6
Drug Content (%)	99	98
Tensile Strength (g/cm²)	11	12
Percent Elongation (%)	9	10
Drug Release (10 min) (%)	92	95

Pharmacokinetics

HPLC analysis confirmed method precision and reproducibility. Plasma drug concentration profiles demonstrated rapid absorption, validating the fast-dissolving film approach as superior to conventional dosage forms.

Table 6: Drug Release Kinetics of Optimized Formulations and Marketed

Formula Code	Zero Order (r²)	First Order (r²)	Higuchi (r²)	Korsmeyer-Peppas (r²)	n Value
F16 (Lazabemide)	0.851	0.988	0.935	0.882	0.376
F18 (Selegiline)	0.937	0.981	0.958	0.934	0.442
Marketed Product	0.823	0.947	0.928	0.718	0.405

FT-IR Studies:

The FTIR spectra of Lazabemide and Selegiline (pure drug, physical mixture, and optimized films) showed that all characteristic peaks of the drugs were retained. Only minor shifts and band broadenings were observed in the films due to the polymer and plasticizer environment. This confirmed the absence of major drug–excipient chemical interactions, indicating good compatibility.

Scanning Electron Microscopy (SEM):

SEM images of Lazabemide (F16) and Selegiline (F18) optimized films revealed rough and uneven surfaces with small pits. The absence of visible crystalline drug particles suggested uniform drug distribution in the polymer matrix and partial conversion into amorphous form, supporting improved solubility and film integrity.

Stability Studies:

The optimized formulations F16 (Lazabemide) and F18 (Selegiline) were subjected to accelerated stability testing at 40 ± 2°C / 75 ± 5% RH for 90 days. Results indicated that both formulations retained their physicochemical integrity throughout the study. Drug content and in-vitro release showed only slight reductions over time but remained within acceptable ICH limits, confirming consistent performance. Disintegration time increased marginally (by 2–3 seconds), yet films still disintegrated rapidly, preserving the intended fast-dissolving property. These findings establish that both optimized films were stable under accelerated storage conditions, ensuring their reliability for therapeutic use.

Stability studies for optimized formulation

Table 7: Physicochemical Characteristics of Optimized Formulations Stored at 40 ± 2ºC / 75 ± 5% RH (Up to 90 Days)

Retest Time	F16 (Lazabemide)			F18 (Selegiline)
Retest Time	Disintegration Time (sec)	Drug Content (%)	In-vitro Drug Release (%)	Disintegration Time (sec)	Drug Content (%)	In-vitro Drug Release (%)
0 days	8	99	99	9	100	100
30 days	9	98	98	10	98	98
60 days	10	98	97	10	97	97
90 days	11	97	97	11	97	96

Both formulations (F16 and F18) maintained stability for 90 days under accelerated conditions. Minor reductions in drug content and release were observed but remained within acceptable limits. Disintegration time slightly increased, indicating good overall stability.

CONCLUSION:

The optimized fast-dissolving oral films of Lazabemide (F16) and Selegiline (F18) were successfully developed using HPMC polymers. Both films exhibited desirable physicochemical and mechanical properties, including uniform thickness, adequate tensile strength, and excellent folding endurance. The surface pH remained close to neutrality, ensuring safety for oral mucosa. Rapid disintegration (8–9 seconds) and nearly complete drug release within 10 minutes confirmed the films’ efficiency in providing quick onset of action. FTIR and SEM results demonstrated no drug–excipient interaction and indicated uniform drug dispersion in an amorphous state. Stability studies further verified the formulations’ robustness under accelerated conditions. Overall, these optimized films present a promising alternative for enhancing bioavailability, patient compliance, and therapeutic efficacy in neuroprotective treatment.

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Finberg JPM, Rabey JM. Inhibitors of MAO-A and MAO-B in psychiatry and neurology. Front Pharmacol. 2016; 7: 340.
Youdim MBH, Bakhle YS. Monoamine oxidase: isoforms and inhibitors in Parkinson’s disease and depressive illness. Br J Pharmacol. 2006;147(S1): S287-S296.
Titova N, Chaudhuri KR. Personalized medicine in Parkinson’s disease: time to be precise. Mov Disord. 2017;32(8):1147-1154.
ZELAPAR® (selegiline HCl) orally disintegrating tablets. US Prescribing Information. Valeant/ANI; current label.
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Riederer P, Laux G. MAO-B inhibitors in Parkinson’s disease: clinical-pharmacological aspects. J Neural Transm. 2011;118(7):963-977.
Lees AJ. Selegiline hydrochloride: a review of its pharmacology and clinical efficacy in Parkinson’s disease. Drugs. 1989;38(5):622-640.
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Birks J, Flicker L. Selegiline for Alzheimer’s disease. Cochrane Database Syst Rev. 2003;(1):CD000442.
Bialer M, et al. Orally disintegrating dosage forms and patient acceptability. Eur J Pharm Sci. 2020;139:105019.
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Gattu Venkata Sravani

Corresponding author

Avanthi Institute of Pharmaceutical Sciences, Hyderabad.

Dr. Mungi Rama Krishna

Co-author

Avanthi Institute of Pharmaceutical Sciences, Hyderabad.

Gattu Venkata Sravani*, Dr. Mungi Rama Krishna, Development and Evaluation of Fast Dissolving Oral Films of Selegiline and Lazabemide for Enhanced Neuroprotection, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 10, 2277-2286 https://doi.org/10.5281/zenodo.17422087

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Development And Evaluation of Fast Dissolving Oral Films of Selegiline and Lazabemide for Enhanced Neuroprotection

Abstract

Keywords

Introduction

Reference

Gattu Venkata Sravani

Dr. Mungi Rama Krishna

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