Comparison of oven drying and freeze drying methods for the production of fast melt films containing quetiapine fumarate.

BACKGROUND: Quetiapine fumarate (QTP) is commonly prescribed for schizophrenic patient, typically available in tablet or oral suspension form, presenting challenges such as administration difficulties, fear of choking and distaste for its bitter taste. Fast melt films (FMF) offer an alternative dosage form with a simple development process, ease of administration and rapid drug absorption and action onset. OBJECTIVE: This study aims to prepare FMF with different formulations using solvent casting methods and to compare the effects of different drying methods, including oven drying and freeze drying, on the properties of the films. METHODS: Various formulations were created by manipulating polymer types (starch, hydroxypropyl methylcellulose (HPMC) and guar gum) at different concentrations, along with fixed concentrations of QTP and other excipients. Characterization tests including surface morphology, weight, thickness, pH, tensile strength, elongation length, Young's modulus, folding endurance and disintegration time were conducted. The optimal FMF formulation was identified and further evaluated for moisture and drug content, dissolution behavior, accelerated stability, X-ray diffraction (XRD), and palatability. RESULTS: FMF containing 10 mg guar gum/film developed using oven drying emerged as the optimum choice, exhibiting desirable film appearance, ultra-thin thickness (0.453 ± 0.002 mm), appropriate pH for oral intake (pH 5.0), optimal moisture content of 11.810%, rapid disintegration (52.67 ± 1.53 s), high flexibility (folding endurance > 300 times) and lower Young's modulus (1.308 ± 0.214). CONCLUSION: Oven drying method has been proven to be favorable for developing FMF containing QTP, meeting all testing criteria and providing an alternative option for QTP prescription.

Fabrication and characterization of orodispersible films loaded with solid dispersion to enhance Rosuvastatin calcium bioavailability.

The present study was aimed to formulate and evaluate fast dissolving oral film of Rosuvastatin calcium to improve its bioavailability in comparison to typical solid oral dosage forms. The drug was formulated as solid dispersion with hydrophilic polymers and assessed for different constraints such as drug content, saturated solubility, and drug-polymer interaction. Best formula was selected and prepared in the form of orodispersible film. The films were developed by solvent casting method and examined for weight variations, drug content, folding endurance, pH, swelling profile, disintegration time, and in vitro dissolution. Further pharmacokinetic study was also performed on rabbit and compared with that of the marketed oral formulation. The drug and the polymers were found to be compatible with each other by FTIR study. Maximum solubility was found at drug polymer ratio of 1:4 and that was 54.53 ± 2.05 µg/mL. The disintegration time of the developed film was observed to be 10 ± 2.01 s, while release of the Rosuvastatin from the film was found to be 99.06 ± 0.40 in 10 min. Stability study shown that developed film was stable for three months. Further pharmacokinetic study revealed that developed orodispersible film had enhance oral bioavailability as compared to marketed product (Crestor® tablets). Conclusively, the study backs the development of a viable ODF of Rosuvastatin with better bioavailability.

Use of fenugreek seed gum in edible film formation: major drawbacks and applicable methods to overcome.

Researching on potential biopolymer sources with the aim of developing edible films with better mechanical and barrier properties has become innovative as it would be a key factor to minimize the use of synthetic polymers in food packaging. Therefore, different biopolymers such as galactomannan have been gaining attention recently. Fenugreek seed gum is a rich source of galactomannan which is minimally researched on its applicability in edible film making. The degree of galactose substitution and polymerization are the main factors that determine the functional properties of galactomannan. A strong and cohesive film matrix cannot be produced from fenugreek seed gum as its molecular interaction is weakened due to the high galactose substitution with a high galactose/mannose ratio, 1:1. Structural modifications of galactomannan in fenugreek seed gum will lead to films with the required mechanical properties. Hence, this review summarizes recent scientific studies on the limitations of fenugreek seed gum as a film forming agent and the specific modification techniques that can be applied in order to increase its film forming capability and performance.

Preparation and evaluation of sublingual film of ketorolac tromethamine.

OBJECTIVE: This research aimed to formulate fast-dissolving sublingual films of Ketorolac tromethamine to improve therapeutic efficacy, patient compliance and overcome the drug's gastrointestinal side effects by avoiding direct contact with the gastric mucosa. METHODS: This research produced Ketorolac tromethamine sublingual film by solvent casting method using a variable ratio of polymer and plasticizer but a fixed quantity of other excipients and solvent ratio to evaluate the effect of these components on the overall formulation. Total 9 (F1 to F9) formulations were prepared where the ratio of Kollicoat®IR as polymer and Polyethylene glycol 400 as plasticizer were 2.0:1, 3.0:1, 4.0:1, 4.0:1, 4.8:1, 5.6:1, 5.33:1, 6.0:1, 6.66:1 respectively. The prepared films were evaluated through morphological and organoleptic properties, weight uniformity, folding endurance, surface pH, thickness, percentage of moisture loss, dispersion, dissolution, and drug content uniformity. Also, API-excipients compatibility was evaluated by FTIR spectroscopy. RESULTS: Formulation-2 (F2) demonstrated better film with optimum folding endurance where the ratio of Kollicoat®IR and Polyethylene glycol 400 was 3.0:1. The film's surface and distribution of polymers and drugs were examined by trinocular microscopic imaging where drug molecule showed uniform distribution which was supported by the assay (100.1%) and content uniformity (100.1 ± 1.97%). Performed dissolution studies showed 99.3% of drug dissolution occurred in just 3 min at pH 6.8. CONCLUSION: Prepared films were found to have thin, fast dispersion and dissolution properties. Therefore, the patients can use the sublingual film to get rapid relief of pain with minimal side effects in the gastrointestinal tract.

3D Printed Poly(𝜀-caprolactone)/Hydroxyapatite Scaffolds for Bone Tissue Engineering: A Comparative Study on a Composite Preparation by Melt Blending or Solvent Casting Techniques and the Influence of Bioceramic Content on Scaffold Properties.

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. Polycaprolactone-based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated so as to improve the scaffolds' mechanical properties and tissue in-growth. In this study, hydroxyapatite is incorporated on polycaprolactone-based scaffolds at two different proportions, 80:20 and 60:40. Scaffolds are produced with two different blending methods, solvent casting and melt blending. The prepared composites are 3D printed through an extrusion-based technique and further investigated with regard to their chemical, thermal, morphological, and mechanical characteristics. In vitro cytocompatibility and osteogenic differentiation was also assessed with human dental pulp stem/stromal cells. The results show the melt-blending-derived scaffolds to present more promising mechanical properties, along with the incorporation of hydroxyapatite. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggests polycaprolactone/hydroxyapatite scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Solvent Casting and UV Photocuring for Easy and Safe Fabrication of Nanocomposite Film Dressings.

The aim of this work was to optimize and characterize nanocomposite films based on gellan gum methacrylate (GG-MA) and silver nanoparticles (AgNPs) for application in the field of wound dressing. The films were produced using the solvent casting technique coupled with a photocuring process. The UV irradiation of GG-MA solutions containing glycerol as a plasticizer and different amounts of silver nitrate resulted in the concurrent crosslinking of the photocurable polymer and a reduction of Ag ions with consequent in situ generation of AgNPs. In the first part of the work, the composition of the films was optimized, varying the concentration of the different components, the GG-MA/glycerol and GG-MA/silver nitrate weight ratios as well as the volume of the film-forming mixture. Rheological analyses were performed on the starting solutions, whereas the obtained films were characterized for their mechanical properties. Colorimetric analyses and swelling studies were also performed in order to determine the AgNPs release and the water uptake capacity of the films. Finally, microbiological tests were carried out to evaluate the antimicrobial efficacy of the optimized films, in order to demonstrate their possible application as dressings for the treatment of infected hard-to-heal wounds, which is a demanding task for public healthcare.

Development of Optimized Sumatriptan-Prochlorperazine Combined Orodispersible Films Without Disintegrant: in vitro, ex vivo and in vivo Characterization.

Sumatriptan succinate and prochlorperazine maleate are a clinically proven combination for treating migraine and associated nausea and vomiting. Classical oral dosage forms are not frequently workable in migraine because of the associated nausea/vomiting, and no effective fixed dose combination is available. Thus, the aim of the study was to optimize a combined sumatriptan-prochlorperazine orodispersible film for rapid release of drugs. Orodispersible films were prepared by solvent casting method using varied amounts of polyvinyl alcohol and glycerol as film former and plasticizer, respectively, along with fixed levels of other ingredients employing central composite design. The optimum film (VF) demonstrated disintegration and total dispersion times as 21 s and 2.3 min, respectively. Tensile strength and Young's modulus were 8.86 ± 0.37 MPa and 24.15 ± 0.07 MPa, respectively. The in vitro T80% of both drugs from the ODF was achieved within 4 min. The film was palatable and disintegrated in 2 min in buccal cavity of human volunteers. Permeation study through goat mucosa demonstrated 100% permeation of both drugs within 15 min. X-Ray diffraction and differential scanning calorimetry supported drugs being amorphous and Fourier transform infrared demonstrated drug-excipient compatibility in optimized film. A judicious combination of sumatriptan succinate and prochlorperazine maleate could be prepared in orodispersible films for the possible relief of migraine.

Extremely Foldable and Highly Porous Reduced Graphene Oxide Films for Shape-Adaptive Triboelectric Nanogenerators.

Here, a thin and foldable porous reduced graphene oxide (rGO) fabricated by a solvent casting method (SC-rGO) is introduced. The SC-rGO is superior to aluminum as a positive triboelectric material in triboelectric nanogenerators (TENGs), significantly enhancing TENG output performance. The film shows extremely foldable features, where it could be folded by 1/16 size. The electrical properties and device performance of SC-rGO are optimized varying thicknesses from 5 to 30 µm. A 30 µm thick TENG with a non-annealed SC-rGO film (STENG) shows the highest output of about 255 µW cm-2 due to its high carrier concentration, low work function, and high surface area. After annealing, STENG performance is optimized with a 10 µm thick SC-rGO because their work functions decreases, while the corresponding carrier concentrations decrease according to the thickness of the SC-rGO films. The SC-rGO films are highly durable and stable, where their output and conductivity show negligible changes after 100 000 cycles of mechanical deformation. A large SC-rGO with a size of 13 × 3 cm2 is fabricated and is attached inside a person's arm to demonstrate the shape-adaptive characteristics. Consequently, 170 V is obtained and it turns on 19 green light emitting diodes by simply touching the STENG.

Effective lightweight, flexible and ultrathin PVDF/rGO/Ba2Co2Fe12O22composite films for electromagnetic interference shielding applications.

In this study, we developed a simple and cost-effective solvent film casting method to fabricate ultrathin, flexible and lightweight polyvinylidenefluoride (PVDF)-based composites that provide high electromagnetic interference (EMI) shielding performance. Y-type barium hexaferrite with general formula Ba2Co2Fe12O22was first synthesized by the sol-gel autocombustion method and then reduced graphene oxide (rGO) was prepared by modified Hummer's method. The crystal structure, morphology, elemental surface analysis and magnetic properties of the samples were systematically investigated using x-ray diffraction spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, high-resolution scanning electron microscopy, energy-dispersive x-ray spectroscopy, x-ray photoelectron spectroscopy and vibrating sample magnetometry. Then, the complex permittivity, complex permeability and EMI shielding properties of the flexible PVDF/rGO/Ba2Co2Fe12O22composite films with two different amounts of Ba2Co2Fe12O22NP content and a fixed amount of rGO content were investigated using a vector network analyzer. The structural characterizations of the resultant composite films showed the formation of an electroactiveß-phase of PVDF with addition of Ba2Co2Fe12O22nanoparticles and rGO content. The enhancement of theß-phase in the PVDF/rGO/Ba2Co2Fe12O22nanocomposites was explained from a physicochemical viewpoint. Furthermore, the electrically conductive and magnetic properties of PVDF composite films incorporating rGO and Ba2Co2Fe12O22NPs exhibited a high EMI shielding effectiveness of 25.63 dB, with an absorption-dominated shielding feature in the 8-12 GHz region. The enhanced absorption was attributed to the electrostatic interaction induced by theß-phase fraction in the PVDF matrix, and subsequently from multiple reflections and magnetic loss originating from the synergetic effect of rGO and Ba2Co2Fe12O22NPs. This study introduces a low-cost and scalable method for the design of novel, lightweight, flexible and efficient EMI shielding composite films with promising prospects for application in the construction, electronics and aerospace fields.

Development of orally dissolving films for pediatric-centric administration of anti-epileptic drug topiramate - A design of experiments (DoE) study.

Children have often been treated as small adults in relation to drug formulation, but research has now shown this not to be the case. Therefore, there is a push from regulatory bodies to provide drug formulations specifically tailored towards the needs of this fragmented population. Orally dissolving films (ODFs) have been identified as an emerging opportunity, to bridge this gap. Therefore, the aim of this study was to prepare ODFs containing topiramate, an antiepileptic drug, using solvent casting method as a potential alternative to oral tablets/powders for paediatrics. For this purpose, a Design of Experiment (DoE) was employed to optimise formulation parameters. 24 formulations were prepared by changing the polymer type (HPMC, Guar-Gum or PEO), concentration (0.4%-1.2%w/v); plasticizer type (glycerol\sorbitol) and concentration (0.1-0.3%w/v). Disintegration time, content-uniformity, film quality and thickness uniformity were the responses. Surface and molecular profiling were conducted on the optimal formulation (N4). TGA and XRD results demonstrated the stability of materials upon production into films, while the SEM images showed smooth films that proved to be resilient due to good mechanical properties. HPMC-glycerine based ODFs are presented as an effective dosage form to enhance the ease of administration and patient compliance of topiramate, specifically for paediatric patients.

Spray-Drying, Solvent-Casting and Freeze-Drying Techniques: a Comparative Study on their Suitability for the Enhancement of Drug Dissolution Rates.

PURPOSE: Solid dispersions (SDs) represent the most common formulation technique used to increase the dissolution rate of a drug. In this work, the three most common methods used to prepare SDs, namely spray-drying, solvent-casting and freeze-drying, have been compared in order to investigate their effect on increasing drug dissolution rate. METHODS: Three formulation strategies were used to prepare a polymer mixture of polyvinyl-alcohol (PVA) and maltodextrin (MDX) as SDs loaded with the following three model drugs, all of which possess a poor solubility: Olanzapine, Dexamethasone, and Triamcinolone acetonide. The SDs obtained were analysed and compared in terms of drug particle size, drug-loading capacity, surface homogeneity, and dissolution profile enhancement. Physical-chemical characterisation was conducted on pure drugs, as well as the formulations made, by way of thermal analysis and infrared spectroscopy. RESULT: The polymers used were able to increase drug saturation solubility. The formulation strategies affected the drug particle size, with the solvent-casting method resulting in more homogenous particle size and distribution when compared to the other methods. The greatest enhancement in the drug dissolution rate was seen for all the samples prepared using the solvent-casting method. CONCLUSION: All of the methods used were able to increase the dissolution rate of the pure drugs alone, however, the solvent-casting method produced SDs with a higher surface homogeneity, drug incorporation capability, and faster dissolution profile than the other techniques.

Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells.

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10-20 µm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 µm), expressed neuron-specific class III ß-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.

Mucoadhesive films based on gellan gum/pectin blends as potential platform for buccal drug delivery.

Films of gellan gum:pectin blends were prepared by solvent casting method. Gellan gum:pectin mass ratios were varied (4:1; 1:1; 1:4) at different concentrations (3% or 4%) and glycerol was used as plasticizer (1 or 2%). The films were thin (18-30 µm), translucent, flexible, and homogeneous. The surface pH was suitable for buccal application. All films reached high mechanical resistance and the mucoadhesive ability of them was evidenced. High ratio of gellan gum improved the mechanical resistance and the mucoadhesion of the films as well as the control of drug release rates. The films did not disintegrate in simulate saliva up to 24 h and curcumin release could be sustained up to 12 h. The set of data evidence that the films designed in this work represent a potential platform for buccal drug delivery.

Characterization and removal of antibiotic residues by NFC-doped photocatalytic oxidation from domestic and industrial secondary treated wastewaters in Meric-Ergene Basin and reuse assessment for irrigation.

Antibiotics are important contaminants that have become an increasingly big problem due to the discharge of the receiving environment. The presence of these organic based pollutants in influent wastewater can inhibit the biological processes and resist to degradation in wastewater treatment plants. Moreover, the consumption of agricultural products, irrigated with water containing antibiotic residues, leads to major harmful effects to the human body through the food chain. In this study; firstly, a conventional characterization was made in terms of COD, TOC, SS, color and of antibiotic residue characterization of untreated raw (influent) and biologically treated (effluent) water from domestic and industrial wastewater treatment plants located in the Meriç-Ergene Basin. After that, photocatalytic activity test was run under visible light for selected antibiotics (Erythromycin, Ciprofloxacin, Sulphametoxasol) which were detected by HPLC MS/MS in excess amount. Finally, for the photocatalytic oxidation, a new generation NFC (Nitrogen-Floride-Carbon)-doped titanium dioxide photocatalyst, which has never been studied in the literature before, was prepared according to the sol-gel method without using thermal processing. Photocatalysts were characterized by UV-vis DRS reflectance and Laser Raman Spectra measurements. All other analyzes were made according to the standard methods. Considering the conventional characterization results; investigated domestic wastewaters exhibited moderate characteristics while industrial wastewater samples had strong characteristics in terms of COD, TOC and SS pollution in accordance with the literature. By the way, contrary to expectations, antibiotic residue results have proved that the effluent wastewater contains more antibiotics than the influent. This can be explained by the fact that, some antibiotics in domestic wastewaters are probably already trapped in feces and cannot be purified by conventional systems since they are released after biological treatment, as mentioned similar studies in the literature. Moreover, by means of 7 h NFC-doped photocatalytic oxidation under visible light, beside approximately % 62 to %79 COD and 62%-86% TOC removal, %99 to %100 removal of antibiotic residue was provided. According to these results, domestic and industrial secondary treated wastewaters in Meric-Ergene Basin can be advance treated, succesfully, with NFC-doped photocatalyst to remove antibiotic residues besides conventional pollutants. This result show that Meriç-Ergene discharge criteria determined by Forest and Water Ministry of Turkey can be provided with this new type photocatalytic process and healthy reuse of this river for irrigation will be possible.

Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug development.

The present study details the development of a small-scale spray-drying approach for the routine screening of amorphous solid dispersions (ASDs). This strategy aims to overcome the limitations of standard screening methodologies like solvent casting and quench cooling to predict drug-polymer miscibility of spray-dried solid dispersions (SDSDs) and therefore to guarantee appropriate carrier and drug-loading (DL) selection. A DoE approach was conducted to optimize process conditions of ProCept 4M8-TriX spray-drying to maximize the yield from a 100 mg batch of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus 40:60 (w/w). Optimized process parameters include: inlet temperature, pump speed, drying and atomizing airflows. Identified process conditions derived from the DoE analysis were further (i) tested with Itraconazole, Naproxen and seven polymers, (ii) adapted for small cyclone use, (iii) downscaled to 20 mg batch production. Drug-polymer miscibility was systematically characterized using modulated differential scanning calorimetry (mDSC). Spray-drying was identified as a well-suited screening approach: mean yield of 10.1 to 40.6% and 51.1 to 81.0% were obtained for 20 and 100 mg ASD productions, respectively. Additionally, this work demonstrates the interest to move beyond conventional screening approaches and integrate spray-drying during screening phases so that a greater prediction accuracy in terms of SDSDs miscibility and performance can be obtained.

Formulation and Evaluation of Novel Thiolated Intra Pocket Periodontal Composite Membrane of Doxycycline.

Localized intra-pocket, retentive, biodegradable, prolonged release thiolated membrane can provide an improved therapeutic efficacy of doxycycline at the site of action with evading off target side effects. To this end, thiolated chitosan-hyaluronic acid composite polymeric complex next-generation of the periodontal membrane was manufactured by solvent casting method. FTIR spectroscopic analysis displayed successful immobilization of thiol groups on the manufactured thiolated periodontal membrane. Moreover, XRD, DSC, AFM and TGA of the membrane confirmed the compatibility of ingredients and modifications in surface chemistry. The thiolated periodontal film was also investigated in terms of thickness, weight uniformity, water-uptake capacity, drug content, pH, entrapment efficiency, lysozymal degradation and release patterns. Also, mucoadhesion profile was explored on gingival mucosa. The immobilized thiol groups on thiolated chitosan and thiolated hyaluronate were found to be 168 ± 11 µM/g (mean ± SD, n = 3) and 189 ± 8 µM/g (mean ± SD, n = 3) respectively. Swelling capacity of the thiolated periodontal membrane was significantly ∼2-fold higher (p < 0.05) as compared to unmodified membrane. The obtained thiolated membrane depicted 3 -old higher mucoadhesive features as compared to the un-modified membrane. In vitro release kinetics indicated approximately more than 80% prolonged release within 7 days. Mechanical strength of the Thiolated bandage was also significantly ∼2-fold higher (p < 0.05) as compared to unmodified membrane. Ex-vivo retention study revealed enhanced retention of thiolated membrane as compared to unmodified membrane. In-vitro antimicrobial studies demonstrated that thiolated membrane could efficiently kill Porphyromonas gingivalis cells as compared to the native membrane. Moreover, ex-vivo biodegradation results indicated that 90% of the thiolated membrane was biodegradable in 28 days. Based on these findings, thiolated next-generation of the periodontal membrane seems to be promising for periodontitis therapy.

Development of Orodispersible Films Containing Benzydamine Hydrochloride Using a Modified Solvent Casting Method.

The aim of this study was to develop benzydamine hydrochloride-loaded orodispersible films using the modification of a solvent casting method. An innovative approach was developed when the drying process of a small-scale production was used based on a heated inert base for casting the film. During this process, two types of film-forming maltodextrins for rapid drug delivery were used. They were plasticized with two different polyols (xylitol and sorbitol). Superdisintegrant Kollidon® CL-F was tested as an excipient that can induce faster disintegration of the prepared films. The influence of the formulation parameters (dextrose equivalent of film-forming maltodextrins, a type of plasticizer, and the presence of superdisintegrant) on the disintegration time, mechanical properties, and moisture content of films was statistically evaluated using a multivariate data analysis. Orodispersible films containing maltodextrin with lower dextrose equivalent value showed better mechanical properties (tensile strength ranged from 886.6 ± 30.2 to 1484.2 ± 226.9 N cm-2), lower moisture content (0.5 ± 0.0 to 1.2 ± 0.2%), and shorter disintegration time (17.6 ± 2.9 to 27.8 ± 2.8 s). Films plasticized with xylitol showed shorter disintegration time (17.6 ± 2.9 to 29.2 ± 3.8 s) than films containing sorbitol (23.8 ± 2.9 to 31.7 ± 3.9 s). With the addition of superdisintegrant Kollidon® CL-F, a significant influence on disintegration time was not observed. The modified solvent casting method shows great promise in a small-scale laboratory production of orodispersible films, e.g., in a pharmacy lab.

Controlled initial surge despite high drug fraction and high solubility.

Potential connections between release profiles and solvent evaporation rates alongside polymer chemistry were elucidated for the release of tetracycline hydrochloride from two different poly (d, l-lactide-co-glycolide) (PLGA) film matrices containing high drug fractions (50%, 30%, and 15%), and prepared at two distinct solvent evaporation rates. At highest tetracycline concentrations (50%), (i) the early release rates were ≤0.5 µg/min in all cases; (ii) release was linear from systems fabricated with lower lactic content and slower solvent evaporation rate and bimodal from systems fabricated with higher lactic content and faster evaporation rate; (iii) surface fractions covered by the drug were similar at both evaporation rates for 85:15 PLGA but very different for 50:50 PLGA, leading to unexpectedly reduced early release from 50:50 PLGA than from 85:15 PLGA when both the matrices were fabricated using a slower evaporation rate. These features remained unaffected in case of low drug concentration. Results suggested that during the formation of the drug-polymer microstructure, the combined effect of polymer chemistry and solvent evaporation rate sets apart the surface characteristics and the initial release profiles of systems containing high drug fraction, and an appropriate combination of these parameters may be utilized to control the early stage of drug release.

Matrix-type transdermal films to enhance simvastatin ex vivo skin permeability.

This study aimed at employing Plackett-Burman design in screening formulation variables that affect quality of matrix-type simvastatin (SMV) transdermal film. To achieve this goal, 12 formulations were prepared by casting method. The investigated variables were Eudragit RL percentage, polymer mixture percentage, plasticizer type, plasticizer percentage, enhancer type, enhancer percentage and dichloromethane fraction in organic phase. The films were evaluated for physicochemical properties and ex vivo SMV permeation. SMV initial, delayed flux, diffusivity and permeability coefficient were calculated on the delayed flux phase with constraint to minimize the initial flux and approaching steady-state flux. The obtained results revealed flat films with homogeneous distribution of SMV within the films. Thickness values changed from 65 to 180 µm by changing the factors' combinations. Most of the permeation profiles showed sustained release feature with fast permeation phase followed by slow phase. Analysis of variance (ANOVA) showed significant effects (p < 0.05) of the investigated variables on the responses with Prob > F values of 0.0147, 0.0814, 0.0063 and 0.0142 for the initial and delayed fluxes, permeability coefficients and diffusivities, respectively. The findings of screening study showed the importance of the significant variables to be scaled up for full optimization study as a promising alternative drug delivery system.

Design and evaluation of mucoadhesive oral films containing sodium hyaluronate using multivariate data analysis.

CONTEXT: Mucoadhesive oral films, with their prolonged residence time at the site of application, offer a promising approach for protection of the oral lesion surface. The addition of sodium hyaluronate of different molecular weights as a second mucoadhesive polymer into the film matrix could positively influence the physico-mechanical and mucoadhesive properties of films. OBJECTIVE: The aim of this study was to investigate the formulation of a monolayered film matrix containing varying amounts of sodium hyaluronate and to test the properties of such matrices by applying different characterization methods. MATERIALS AND METHODS: Film matrix was composed of two mucoadhesive polymers, carmellose sodium and sodium hyaluronate, plasticized with glycerol. Resulting films were characterized with regard to their viscosity and physico-mechanical properties. RESULTS AND DISCUSSION: Multivariate data analysis was employed to evaluate the influence of varying amounts of mucoadhesive polymers on the main mucoadhesive oral films' properties. The lower content of sodium hyaluronate caused improvements in mechanical properties and residence time on the artificial oral mucosa, both of which are the main characteristics that determine the quality of the final product. CONCLUSIONS: The best results were obtained by samples containing carmellose sodium with a small amount of sodium hyaluronate (about 0.5% in casting dispersion).