Film-forming Polymers Research Articles

Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film

The utilization of zein and gum arabic has grown in an attempt to formulate wall materials based on protein–polysaccharide complexes. This mixture provides a versatile delivery system for hydrophilic (guava leaf extract, GLE) or lipophilic (fish oil, FO) bioactive compounds, and it can be used as an edible film-forming polymer. This study was undertaken to characterize FO-containing edible films that were double-layered with a film containing GLE. Modified zein and gum arabic solutions (MG complex) were mixed at a ratio of 1:1.5 (v/v), adjusted to pH 5, added with glycerol (20% of the complex) and FO (5% of the complex), and finally adjusted to pH 5. This was prepared as the bottom/lower layer. The upper/active layer was prepared by mixing MG complex, glycerol, and GLE (1, 3, and 5% w/v of the complex). The total phenolic and flavonoid contents in GLE were 15.81 mg GAE/g extract and 6.99 mg QE/g extract, respectively. The IC50 of the DPPH radical scavenging activity of GLE was 26.86 ppm with antibacterial activity against Bacillus subtilis and Escherichia coli of 9.83 and 12.55 mm. The total plate counts of double-layered films containing GLE were retained below 3 log CFU/g during 28-day storage. The peroxide values of these films were dimmed for no more than 9.08 meq/kg sample on day 28 of storage. Thickness (872.00-971.67 μm), water vapor transmission rate (12.99-17.04 g/m2/day), tensile strength (1.56-2.02 kPa), elongation at break (61.53-75.41%), glass transition (52.74-57.50°C), melting peak (131.59-142.35°C), inhibition against B. subtilis (33.67-40.58 mm), and inhibition against E. coli (2.05-9.04 mm) were obtained by double-layered films. GLE can be successfully incorporated into the active layer of a double-layer film to improve its characteristics while significantly slowing down the microbial contamination and oxidation rate. MG complex and FO can also contribute to the performance of the edible film.

Pharmacokinetic Study of Fingolimod Nasal Films Administered via Nose-to-Brain Route in C57BL/6J Mice as Potential Treatment for Multiple Sclerosis.

Fingolimod hydrochloride (FH) has emerged as a vital medication for managing Multiple Sclerosis (MS). Despite its high oral bioavailability of 93%, it is plagued by slow oral absorption (Tmax = 8-12h) and extensive hepatic metabolism. Intranasal administration has emerged as an alternative to address these limitations, ensuring efficient central nervous system delivery and minimizing peripheral exposure and first-pass metabolism. This study aims to develop and evaluate FH nasal films for enhanced drug delivery. A Design of Experiments approach was employed to formulate FH nasal films, utilizing HPMC E50 as a film-forming polymer, PEG 400 as a plasticizer, and Me-β-CD as a permeation enhancer. Two formulations with superior in vitro and ex vivo performance were selected for in vivo evaluation. A comparative pharmacokinetic study was conducted in C57BL/6J mice in the brain and serum after administration of nasal films and oral FH solution, respectively. Sparse sampling and non-compartmental analysis were used. FH nasal films efficiently delivered the drug to both serum (Cmax(F3) = 0.35 ± 0.021, Cmax(F4) = 0.38 ± 0.029μg/mL) and brain (Cmax(F3) = 0.39 ± 0.05, Cmax(F4) = 0.44 ± 0.048μg/mL), achieving higher levels than oral delivery. Brain relative bioavailability (% Frel (0-6 h)) was 519% and 534%, while serum % Frel (0-6 h) was 295% and 343%. The rapid nose-to-brain delivery within 30min, in contrast to 10-h Tmax of the oral solution, indicates the potential of a combined IN and oral treatment regimen. This approach could expedite the attainment of steady-state concentrations, offering a promising method for managing multiple sclerosis (MS).

Design and in vitro/in vivo evaluation of chitosan-polyvinyl alcohol copolymer material cross-linked by dynamic borate ester covalent for pregabalin film-forming delivery system

This research introduced a novel polymer synthesized by combining chitosan and modified polyvinyl alcohol, cross-linked with boric acid using dynamic covalent bonds. The polymer was developed to formulate a pregabalin Film-forming system (FFS) for treating postherpetic neuralgia via topical application, showcasing notable skin adhesion and drug delivery properites. The chitosan-boric acid-modified polyvinyl alcohol polymer was analyzed using NMR, FTIR. The exceptional features of the optimized FFS were evaluated through rheometer, Differential scanning calorimetry (Tg = 45.98 °C), contact angle (θ = 78.62°). The elongation (60.05 ± 3.67 %), cohesion (56.94 ± 4.65 MPa) and skin adhesion (58.12 ± 2.99 kPa) of chitosan-boric acid-modified polyvinyl alcohol were found to be 5.2, 6.8, and 8.3 times higher than those of the pure chitosan film, attributed to the double network structure formed by the cross-linked reversible dynamic covalent bond. The optimized pregabalin FFS exhibited increased in vitro (86.25 ± 1.87 μg/g) and in vivo (100.42 ± 7.44 μg/g) skin retention amounts compared to in vivo oral administration (28.43 ± 4.61 μg/g). In summary, the utilization of borate ester dynamic covalent bonds in developing chitosan-based film-forming polymer proved beneficial in improving skin adhesion and topical therapeutic effectiveness, thereby mitigating the risk of systemic side effects associated with oral administration.

An Overview of the Components, Techniques, and Innovation Used for Fast-Dissolving Films.

Fast-dissolving films (FDFs) stand as a cornerstone in modern pharmaceutical innovation, heralded for their unrivaled convenience, patient adherence, and the swift onset of action. Within the realm of this paper lies a meticulous exploration of FDFs, delving deep into their intricate formulation intricacies, manufacturing methodologies, and diverse therapeutic applications. The formulation journey traverses the meticulous selection of film-forming polymers, plasticizers, taste-masking agents, and active pharmaceutical ingredients (APIs), each element meticulously calibrated to achieve optimal efficacy. Diverse production techniques, spanning solvent casting, hot melt extrusion, and spray drying, are scrutinized with precision, shedding light on their inherent advantages and nuanced limitations. Beyond the realm of formulation and manufacturing, this review embarks on an expansive voyage into the vast therapeutic landscape that FDFs traverse. From the treatment areas of central nervous system disorders to the realms of cardiovascular diseases, allergies, and pain management, the versatility and adaptability of FDFs emerge as a beacon of hope for patients and practitioners alike. Yet, amidst the brilliance of FDFs, inherent challenges linger, from stability concerns to the intricate dance of bioavailability and the ever-watchful eye of regulatory scrutiny. However, within these challenges lies the fertile ground for future research and development endeavors, beckoning forth a new era of innovation and advancement in the realm of rapidly dissolving films. This study stands as an indispensable compass, guiding researchers, pharmaceutical scientists, and practitioners toward the forefront of FDF development and implementation.

Assessing α-Bisabolol as a Transmucosal Permeation Enhancer of Buccal Local Anesthetics.

Needle-free buccal anesthesia improves dental treatment outcomes for both patients and dentists. In this study, we report on an assessment of the enhancement effects of α-bisabolol on the in vitro transmucosal permeation of prilocaine hydrochloride (PCl) and lidocaine hydrochloride (LCl) from needleless buccal films. We also evaluated the mechanical properties of the film, which consisted of Methocel™ K100 LV as the film-forming polymer (3% m·m-1), PEG 400 as a cosolvent (15% m·m-1 based on drug loading), α-bisabolol (15 and 30% m·m-1 based on drug loading), and the drugs combined at a 1:1 ratio (15 mg·unit-1). The porcine esophageal epithelium was used as a membrane barrier, and artificial saliva was the release medium. After a 1 h experiment at 25 ± 2 °C, α-bisabolol significantly decreased, rather than enhanced, the permeation fluxes (five-fold), permeability coefficients (seven-fold), and retentions (two-fold) of both PCl and LCl through the epithelium, regardless of the concentration. Moreover, the resistance and flexibility of the films markedly decreased compared to those without α-bisabolol. Therefore, under the experimental conditions, using α-bisabolol as a buccal permeation enhancer for the hydrophilic local anesthetics PCl and LCl from buccal films is not feasible.

Design, In-Vitro Characterization and Optimization of Fast Dissolving Sublingual Film containing Aripiprazole

The present research work aim was to formulate a fast-dissolving sublingual film containing Aripiprazole, which is used in the treatment of schizophrenia and bipolar disorder. Fast Dissolving Sublingual Film Containing Aripiprazole prepared by using the solvent casting method. Aripiprazole is a BCS IV drug with poor solubility and poor permeability causing poor systemic absorption. Fast dissolving sublingual film prepared by using Design-Expert® version13 software with 32 full factorial designs in which Film-forming polymer HPMC K4M and plasticizers like PEG 400, and PVA are used in different concentrations. The formulated batches was evaluated for mechanical properties, surface pH, folding endurance, drug content, swelling property, SEM analysis, and in vitro % drug release. The characterization of the film shows satisfactory results following mechanical properties of a film like weight variation and thickness. The formulation (F4, F12) containing the highest concentration of plasticizer shows a high folding endurance ranges from 90-100%. FTIR and DCS studies reveal that there are no interactions means drugs and excipients are compatible with each other. Formulation F4 is optimized batch passes evaluation parameters and maximum % drug release i.e. 98.79 % ±0.36 within 1.5 min. Therefore, the sublingual film is an effective approach for BCS IV and III class drugs by avoiding first-pass metabolism with rapid onset of action and better patient compliance in psychotic disorders.

Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film

Background The utilization of zein and gum arabic has grown in an attempt to formulate wall materials based on protein–polysaccharide complexes. This mixture provides a versatile shelter for hydrophilic (guava leaf extract, GLE) or lipophilic (fish oil, FO) bioactive compounds from unwanted environmental factors, and it can be used as an edible film-forming polymer. This study was undertaken to characterize FO-containing edible films that were double-layered with a film containing GLE. Methods Modified zein and gum arabic solutions (MG complex) were mixed at a ratio of 1:1.5 (v/v), adjusted to pH 5, added with glycerol (20% of the complex) and FO (5% of the complex), and finally adjusted to pH 5. This was prepared as the bottom/lower layer. The upper/active layer was prepared by mixing MG complex, glycerol, and GLE (1, 3, and 5% w/v of the complex). Physical, mechanical, microstructural, thermal, microbiological, and oxidative measurements were also performed. Results The total phenolic and flavonoid contents in GLE were 15.81 mg GAE/g extract and 6.99 mg QE/g extract, respectively. The IC50 of the DPPH radical scavenging activity of GLE was 26.86 ppm with antibacterial activity against Bacillus subtilis and Escherichia coli of 9.83 and 12.55 mm. The total plate counts of films double-layered with a film containing GLE were retained below 3 log CFU/g during 28-day storage. The peroxide values of these films were dimmed for no more than 9.08 meq/kg sample on day 28 of storage. Thickness (872.00-971.67 μm), water vapor transmission rate (12.99-17.04 g/m2/day), tensile strength (1.56-2.02 kPa), elongation at break (61.53-75.41%), glass transition (52.74-57.50°C), melting peak (131.59-142.35°C), inhibition against B. subtilis (33.67-40.58 mm), and inhibition against E. coli (2.05-9.04 mm) were obtained by double-layer films. Conclusions GLE can be successfully incorporated into the active layer of a double-layer film to improve its characteristics while significantly slowing down the microbial contamination and oxidation rate.

Integrated In Vivo and In Vitro Evaluation of a Powder-to-Hydrogel, Film-Forming Polymer Complex Base with Tissue-Protective and Microbiome-Supportive Properties.

The study aimed to perform a comprehensive in vitro and in vivo evaluation of a newly developed, patent-pending, powder-to-hydrogel, film-forming polymer complex base, which possesses tissue-protective and microbiome-supportive properties, and to compare its characteristics with poloxamer 407. The study used a combination of in vitro assays, including tissue viability and cell migration, and in vivo wound healing evaluations in male diabetic mice. Microbiome dynamics at wound sites were also analyzed. The in vitro assays demonstrated that the polymer complex base was non-cytotoxic and that it enhanced cell migration over poloxamer 407. In vivo, the polymer complex base demonstrated superior wound healing capabilities, particularly in combination with misoprostol and phenytoin, as evidenced by the reduced wound area and inflammation scores. Microbiome analysis revealed favorable shifts in bacterial populations associated with the polymer complex base-treated wounds. The polymer complex base demonstrates clinical significance in wound care, potentially offering improved healing, safety and microbiome support. Its transformative properties and efficacy in drug delivery make it a promising candidate for advanced wound care applications, particularly in chronic wound management.

Cellulose- and Saccharide-Based Orally Dispersible Thin Films Transform the Solid States and Dissolution Characteristics of Poorly Soluble Curcumin.

This study aimed at developing and optimizing the orally dispersible thin film (ODTF) containing a plant-derived drug-curcumin (CUR). CUR belongs to a biopharmaceutical classification system (BCS) class IV compound that requires improving its water solubility and tissue permeability preceding formulation. An ODTF was applied to produce a solid dispersion matrix for CUR to resolve such solubility and permeability problems. The film-forming polymers used in the study were cellulose-based (hydroxypropyl methylcellulose/HPMC and carboxymethylcellulose/CMC) and saccharide-based maltodextrin (MDX). Poloxamer (POL) was also employed as surfactant and solubilizer. The solvent casting technique was applied to produce the films. The ethanolic solution of CUR was mixed with an aqueous solution of POLs and then incorporated into different film-forming polymers prior to casting. The processing of the CUR with POL solution was intended to aid in the even dispersion of the drug in the polymeric matrices and enhance the wettability of the films. The physical state and properties of the films were characterized in terms of their morphology, crystallinity of the drug, and phase miscibility of the mixtures. The dissolution profile of the films was also evaluated in terms of dissolution rate and dissolution efficiency. The obtained ODTF products were smooth and flat-surfaced. Physical characterization also indicated that the CUR was homogeneously dispersed in the ODTFs and no longer existed as crystalline material as revealed by X-ray diffraction (XRD). The CUR was also not phase-separated from the films as disclosed by differential scanning calorimetry (DSC). Such dispersion was achieved through the solubilizing effect of POLs and compact polymeric film matrices that prevented the CUR from recrystallization. Furthermore, the ODTFs also improved the dissolution of CUR by 3.2-fold higher than the raw CUR. Overall, cellulose-based films had favorable physical properties compared with saccharide-based films.

DEVELOPMENT AND EVALUATION OF DOMPERIDONE ORAL FILM USING MIXED SOLVENCY CONCEPT

a *, a and a a * For Correspondence: E-mail: kirtitomarmip@gmail.com https://doi.org/ ABSTRACT This study aimed to develop and evaluate oral film of antiemetic drug-using mixed solvency concept. The mixed-solvency concept was used in the solubility enhancement of domperidone, an antiemetic drug that is practically insoluble in water. Different types of solubilizers have been used for solubility improvement of domperidone and poly ethylene glycol, niacinamide, caffeine were found to be effective. Five formulations were prepared by using HPMC E15 a film-forming polymer. The prepared oral films were subjected to evaluation for thickness, pH, drug content, folding endurance, stability and in vitro drug release profile. The % in vitro drug release of the best two formulations F3 and F5 were 90.70% and 96.62 % respectively. From the above study, it was concluded that the solubility of the practically insoluble drug, domperidone could be improved successfully by using different water-soluble solubilizers in different ratios under the mixed-solvency concept.

Sweeteners in Orodispersible Films: How Much is too Much?

Four natural sweeteners (sucrose, xylitol, fructose, and isomalt) were selected to examine the influence of their qualities and amounts on the characteristics of orodispersible films. Sodium carboxymethylcellulose (2% w/w) was utilized as the film-forming polymer and 1% w/w glycerol as a plasticizer. Films were produced through the solvent casting method, rendering them suitable for convenient application in community or hospital pharmacy settings. The physicochemical and optical properties of the films were analyzed, and Fourier-transform infrared analysis was carried out. All films exhibited acceptable disintegration time, uniformity of mass, thickness, and optical characteristics, with significant dependence (p<0.05) on both sweetener type and quantity. Disintegration time varied based on the employed method, as well as the characteristics and amount of sweetener. Additionally, all films maintained pH values within the oral cavity range, suggesting no potential irritancy upon administration. Fourier-transform infrared analysis confirmed the formation of the film and demonstrated compatibility between its components.

Film-forming polymer solutions containing cholesterol myristate and berberine mediate pressure ulcer repair via the Wnt/β-catenin pathway.

Pressure ulcer (PU) is a worldwide problem that is difficult to address because of the related inflammatory response, local hypoxia, and repeated ischaemia/reperfusion, causing great suffering and financial burden to patients. Traditional Chinese medicine turtle plate powder can treat skin trauma, but its composition is complex and inconvenient to use. Here, we combined cholesterol myristate (S8) with berberine (BBR), with anti-inflammatory and antibacterial effects, as a drug and used hydroxypropyl methylcellulose and polyvinylpyrrolidone K30 as carriers to construct a novel film-forming polymeric solution (S8 + BBR FFPS), comprehensively study its reparative effect on PU and explore the potential mechanism in rat PU models. The results showed that S8 + BBR FFPS inhibits excessive inflammatory response, promotes re-epithelialization, and promotes hair follicle growth during the healing process of PU, which may be related to the activation of the Wnt/β-catenin signalling pathway by S8 + BBR FFPS to mediate hair follicle stem cell proliferation and maintain skin homeostasis. Therefore, S8 + BBR FFPS may be a potential candidate for the treatment of chronic skin injury, and its association with the Wnt/β-catenin signalling pathway may provide new ideas to guide the design of biomaterial-based wound dressings for chronic wound repair.

Correlation between Optical Characteristics of Orodispersible Films with Selected Process Parameters Supported by FTIR Analysis

Paediatric and geriatric populations, as well as other special patient populations with swallowing problems, require patient-tailored dosage forms. One promising dosage form for these specific populations is orodispersible films.&lt;br /&gt; When preparing orodispersible films using sodium carboxymethyl cellulose as the film-forming polymer and glycerine as the plasticizer, it is essential to determine the optimal mixing time and mixing speed of the casting solution to achieve the desired transparency/opacity of the orodispersible films. In this paper, the primary focus is on mixing time and mixing speed, and determining how these two parameters can influence optical characteristics. All tested parameters are supported by FTIR analysis. The obtained results show that either a mixing speed of 7000 rpm on a high-shear mixer for 15 min or a mixing speed of 9000 rpm for 5 min can produce films with optimal optical characteristics.

Radiation polymerization for the preparation of universal coatings: remarkable anti-fogging and frost-resisting performance.

Hydrophilic anti-fogging coatings have attracted considerable attention due to their ease of preparation and excellent fog resistance. In this study, a hydrophilic anti-fogging coating based on the random copolymer p(AA-co-SAS) was prepared using acrylic acid (AA) and sodium allylsulfonate (SAS) as monomers through radiation polymerization. The introduction of SAS successfully transformed the random copolymer from a gel state into a film-forming polymer solution. The presence of AA structural units in p(AA-co-SAS) improved the film-forming properties of the polymer solution. Additionally, there was a positive correlation between the proportion of SAS structural units in the random copolymer and the scratch hardness and wetting properties of the coating. After coating polycarbonate (PC) sheets, the surface hydrophilicity was significantly enhanced, with the contact angle of PC-AA10/SAS5 decreasing from 100.1° to 18.8° within 50 seconds. The outstanding wetting properties endowed the coating with exceptional anti-fogging and frost-resisting performance. It exhibited optimal transparency under both testing conditions and demonstrated good stability during cyclic testing. Tape adhesion tests indicated that the adhesion between the coating and PC reached a 5B level. When AA10/SAS5 was applied to PET film, glass, and PMMA goggles, all samples showed excellent anti-fog performance. Even after being naturally placed for one year under ambient conditions, the PMMA goggles still maintained good performance in the anti-fog and frost resistance tests. The remarkable comprehensive properties of the polymer coating based on p(AA-co-SAS) suggest enormous potential applications in industries such as packaging, healthcare, and optical equipment.

Film-forming polymer nanoparticle strategy for improving the passivation and stability of perovskite solar cells

Highly deformable crosslinked polymer particles enhance perovskite solar cell passivation and stability by binding and distributing throughout the film.

Construction of decorative, antibacterial, anti-aging and fire-retardant integrative coatings for wood substrates with super protective performances

To prevent the coatings applied in historical buildings from aging failure due to environmental factors, an integrative coating with decorative, antibacterial, weather-resistant and flame-retardant properties is particularly important in practical applications. The nanocomposite flame retardants named CPPBs are obtained from the successful grafting of the phosphate esters to the surface of cerium oxide nanoparticles, which are physically blended with film-forming polymer to construct integrative coating named MCPPBs. The results show that adding nano-CeO2 greatly strengthens the mechanical property, fire protection performances, weather resistance, antibacterial activity of the integrative coatings, and maintains high light transmittance in the meantime. Especially, when the addition of nano-CeO2 in flame retardant is 0.5 wt.%, the expansion ratio of the MCPPB3 coating increases to 65 and the char index reduces to 15.7cm3, concomitant with a high transparency of 80.3 %. By combining FTIR, SEM and EDS analyses, the MCPPBs char containing nano-CeO2 is compact and dense. In the accelerated aging test, the back equilibrium temperature of the MCPPB3 coating at 900 s is still less than 220 °C concomitant with a complete surface morphology after 6 aging cycles. In addition, the MCPPB3 coating exerts a negative effect on the growth of E. coli and S. aureus, and the antibacterial activities against E. coli and S. aureus are 92.8 % and 96.2 %, respectively.

Formulation and evaluation of buccal film of an antihypertensive drug

The aim of the study was to formulate and evaluate Losartan potassium buccal films, an angiotensin receptor blocker and is used to treat hypertension. Losartan potassium is having less bioavailability (33%), so the buccal films are expected to increase the bioavailability by avoiding hepatic metabolism. Ten formulations of buccal films were prepared by solvent casting method using HPMC K15 M as the main film-forming polymer in various proportions with various co-polymers such as Eudragit RL. 100, Carbopol 940, Ethyl cellulose. Physicochemical characteristics,in vitro buccal permeation, in vitro release study and residence time were evaluated. In vitro studies revealed that the release rate of Losartan potassium was higher for films containing HPMC K15 M and Eudragit RL100 in 3:1 ratio. The result of stability study indicated that no significant changes have occurredduring the period of study.

Graphene thermally modified with polyvinyl alcohol applied as conductive water-based paints based on polyurethane

This paper presents the fabrication of thermally reduced graphene modified with polyvinyl alcohol (PVA), which can be used as a conductive water-based paint based on polyurethane (PU). Graphite oxide (GO) was oxidised from graphite by the Hummer method, and then graphene was formed by the thermal-reducing GO method. The graphene was modified by dispersing it into a PVA solution with various concentrations and mass ratios to optimise the modification process. The graphene modified with PVA could be easily dispersed in water. Water-borne PU film-forming polymer was prepared by polymerisation reaction between isophorone diisocyanate with poly(tetramethylene glycol) and dimethylolpropionic acid. The carboxylate functional groups on the surface of the polymer particles make the polymer particles dispersed well and stable in water, so this polymerisation process does not use any surfactants. The characterisation methods included field emission scanning electron microscope with energy-dispersive X-ray spectroscopy (FESEM-EDX), specific surface area measurement, Raman microspectroscopy, resistance measurement... The graphene-based conductive paint has good adhesion, conductivity of the dry paint film was from 0.1-4 mS/cm with graphene content in the dry paint film was about 5-10 wt%.

Development and Evaluation of Pullulan Based Mouth Dissolving Film of Furosemide

Mouth dissolving oral film is an innovative approach as Oromucosal route for systemic delivery of therapeutically/medicinally active drug substance. As we know Furosemide belongs class IV in BCS classification of drug, having low solubility and permeability due to the presence of strong inter and intramolecular bond. Due to low aqeous solubility, it exhibits low oral bioavailability. Here we are preparing mouth dissolving film of furosemide to increase its solubility, which ultimately will enhance its bioavailability. By this way, we will achieve more rapid drug absorption, desired pharmacological effect with quick onset of action by avoiding degradation in GIT and first pass metabolism. This system will provide maximum therapeutic efficacy and maximum stability by reducing the frequency of dosage and as well as improve patient compliance. The present research aimed to prepare pullulan based mouth dissolving oral films of furosemide used in treatment and control of hypertension. Pullulan was selected as film former exhibit better moisture retention, oxygen barrier and uniform film forming properties. Due to the hydrophilic nature of pullulan, it provides quick dissolution. By considering above points, the film was prepared through solvent casting method by pullulan as film-forming polymer, glycerol as plasticizer and lepidium sativum mucilage as a natural disintegrant known as Asaliyo. Disintegration time, drug release, moisture loss and folding endurance of film were evaluated. Promising batch F6 exhibited better drug dissolution 98.75±0.09% within 8±0.4 minutes than the other films. The disintegration time for batch F6 was 23±5 sec. It is evident from the above results that it is an innovative dosage form to improve the drug delivery, onset of action as well as improve patient compliance.

FORMULATION AND EVALUATION OF TACROLIMUS LOADED TRANSFERSOMAL SUBLINGUAL FILMS FOR EFFICIENT MANAGEMENT OF ORGAN REJECTION: IN VITRO AND IN VIVO STUDY

Objective: Patients travailing with end-stage organ failure can benefit from a life-saving treatment protocol called organ transplantation that also rallies eminence of life. Tacrolimus plays an important role in maintaining the healthy status of the organ transplanted, but its widespread clinical application is constrained due to low oral bioavailability which can be the limiting factor for the reduction in life span of transplanted healthy organ. Methods: To overcome the drawbacks of tacrolimus and to maximize its therapeutic efficiency, tacrolimus was formulated as transfersomes using thin film hydration method using soyalecithin and Tween-80, optimized by Central composite designs and characterized for Particle size, deformability index (DI), entrapment efficiency(EE%) and Zeta potential. The selected transfersome formulation was incorporated into sublingual films using Hydroxy Propyl Methyl Cellulose (HPMC) as a film-forming polymer and Polyethylene Glycol (PEG-400) as Plasticizer. The physical characteristics (average weight, pH, uniformity of weight and thickness) of the prepared films were studied, in addition they were evaluated for the in vitro drug release, ex vivo permeation, Differential Scanning Calorimetry (DSC), Attenuated Reflectance Spectroscopy (ATR), Scanning Electronic Microscopy (SEM), stability and in vivo pharmacokinetics in rats to prove the effect of flexibility provided by vesicle formation through sublingual route for enhanced systemic availability of tacrolimus. Results: Designed and optimized transfersomal vesicles showed the vesicle size of 139±2.1 nm with a Deformability Index of 8.53±1.9%, Entrapment Efficiency of 86.66±1.2% and zeta potential of-23.6 mV respectively. Optimized Tacrolimus-loaded transfersomal vesicles (TAC-TFs) showed controlled release with more than 80±3.4% for an extended period of time compared to pure drug Tacrolimus. The average weight of all prepared transfersomal sublingual film (TAC_TF_SL films), batches were found in the range of 55.8±1.45 to 94.2±1.42 mg with mean thickness in the range of 0.23+0.1 to 0.52±0.2 mm indicating uniform cast of respective batches. The surface pH was found to be in the range of 6.9 to 7.0 which was close to saliva pH. Optimized transfersomal sublingual films as well as nanovesicular dispersions found to be followed Zero order diffusion coupled with polymer relaxation. Ex vivo studies revealed the improved permeation of 6.51±0.04µg drug through sublingual mucosa than pure drug of 1.2±0.01 µg, depicting the significant role of soyalecithin and edge activator in the formulations. Transfersomal sublingual films exhibited controlled release with higher plasma concentration of 9.16±2.34 µg/ml at Tmax of 1.29±1.51h in comparison with 7.99±1.23 µg/ml at Tmax of 0.75±1.78h (oral marketed dosage form Pengraf capsules) embarking the higher rate of controlled absorption after sublingual delivery of optimized sublingual films with significant increase in AUC of 129.87±2.40 μg/ml/h when compared to AUC of marketed dosage form of 69.19±1.46 μg/ml/h. In addition, the absolute bioavailability of the drug following sublingual administration was found to be 70.77±2.92% in comparison with that after oral administration 40.60±2.34%. Conclusion: Designed Tacrolimus loaded transfersomal sublingual films can be a promising carrier for delivering tacrolimus through sublingual route by enhancing drug bioavailability efficiently, which can be a boon to organ-transplanted patients.