Investigating a new approach to film casting for enhanced drug content uniformity in polymeric films

Films prepared by conventional casting onto trays such as teflon-coated perspex trays (TCPTs) suffer from poor drug content uniformity. The aim of this study was to prepare a silicone-molded tray (SMT) with individual wells for film casting and to evaluate it in terms of enhancing drug content uniformity. Films were prepared by solvent evaporation or emulsification and cast onto TCPT and SMT. Preparation of films by the SMT method was superior in terms of meeting drug content uniformity requirements. As compared with the TCPT method, the SMT casting method also reduced the variability in mucoadhesivity, drug release, and film thickness. Reproducibility of the SMT method was demonstrated in terms of drug content, mucoadhesion, and drug release.     

Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement

The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting–drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan–SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most?<3% RSD) despite containing only 0.3–1.3?mg drug, which was ensured by the use of precursor suspensions with?>5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t₈₀?相似文献   

Loratidine buccal films for allergic rhinitis: development and evaluation

The objective of this study was to develop a novel patient compliant buccoadhesive film capable of providing a prolonged protection against allergic symptoms. Polymeric buccoadhesive films of loratidine were prepared using hydroxypropylmethyl cellulose (HPMC)-E5 and K100 blend and Eudragit® NE 30D as retardant. Films were prepared using solvent-casting method. The developed films were evaluated for physical properties, hydration, mucoadhesion time, drug release, etc. All the prepared films exhibited excellent mechanical strength and uniform drug content. Increase in drug content did not influence the physicomechanical properties of the film. The mucoadhesive strength of films was significantly enhanced with increase in HPMC content. Increase in Eudragit® NE 30 D content in the film decreases the hydration, erosion and drug release, but enhances the mucoadhesion time. Furthermore, the release of loratidine from the prepared films followed Hixson–Crowell kinetics. Studies in healthy human volunteers using placebo films indicate that the prepared films possess prolonged mucoadhesion in-vivo, and this could potentially lead to clinically relevant drug delivery system.     

Design of antihistaminic transdermal films based on alginate–chitosan polyelectrolyte complexes: characterization and permeation studies

The purpose of this study was to develop suitable matrix-type transdermal drug delivery systems of Ketotifen fumarate (KF) as antiasthmatic drugs. Chitosan–alginate polyelectrolyte complex (PEC) films were used as drug release regulators for KF. Antihistaminic films with variable PEC compositions were prepared using different ratios of chitosan (CTS) to sodium alginate (ALG). Propylene glycol (PG) was used as plasticizer; Tween 80 (T₈₀) and Span 20 (S₂₀) were used as permeability enhancers. Nine formulations were obtained by film casting method and characterized in terms of weight uniformity, thickness, folding endurance, moisture lost, and moisture absorption. In addition, drug release and permeation through rat abdominal skin mounted in Franz cell were investigated. All formulations were found to be suitable in terms of physicochemical characteristics, and there was no significant interaction between the used drug and polymers. It was noticed that when T₂₀ is used as permeation enhancer, a satisfactory drug release pattern was found where 99.88% of drug was released and an amount of 2.121?mg/cm² of KF was permeated after 24?h. For the optimal formulation, a permeability coefficient of 14.00?±?0.001?cm h^?1 and a latency time of 0.35?±?0.02?h were found. The in-vitro analysis showed controlled release profile which was fitted by Korsmeyer–Peppas model (R²?=?0.998). The obtained results suggested that new controlled release transdermal formulations of asthmatic drugs could be suitably designed as an alternative to the common forms.     

Evaluation and controlled release characteristics of modified xanthan films for transdermal delivery of atenolol

The present study was performed to evaluate the possibility of using modified xanthan films as a matrix system for transdermal delivery of atenolol (ATL), which is an antihypertensive drug. Acrylamide was grafted onto xanthan gum (XG) by free radical polymerization using ceric ion as an initiator. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated the formation of the graft copolymer. The obtained graft copolymer was loaded with ATL and films were fabricated by solution casting method for transdermal application. Various formulations were prepared by varying the grafting ratio, drug loading, and different penetration enhancers. The formulations prepared were characterized for weight, thickness uniformity, water vapor transmission rate, and uniformity in drug content of the matrix. All the thin films were slightly opaque, smooth, flexible, and permeable to water vapor, indicating their permeability characteristics suitable for transdermal studies. Fourier transform infrared spectroscopy and differential scanning calorimetry studies indicated no significant interactions between drug and polymer. Drug is distributed uniformly in the matrix but showed a slight amorphous nature. Drug-loaded films were analyzed by X-ray diffraction to understand the drug polymorphism inside the films. Scanning electron microscopic studies of the placebo and drug-loaded films demonstrated a remarkable change in their surface morphology. The skin irritation tests were performed in mice and these results suggested that both placebo and drug-loaded films produced negligible erythema and edema compared to formalin (0.8% v/v) as the standard irritant. The in vitro drug release studies were performed in phosphate buffer saline using a Keshary-Chien diffusion cell. Different formulations were prepared and variations in drug release profiles were observed. Release data were analyzed by using the Ritger and Peppas equation to understand the mechanism of drug release as well as the estimation of n values, which ranged between 0.41 and 0.53, suggesting a Fickian diffusion trend.     

Fast release of liquid antisolvent precipitated fenofibrate at high drug loading from biocompatible thin films

Motivated by recent papers on nano and micro-particle slurry casting of poorly water-soluble drugs forming biocompatible films with enhanced properties, this work explores incorporation of liquid antisolvent (LAS) precipitated suspensions of fenofibrate, a model poorly soluble drug using both semi-synthetic (HPMC E15 LV) and natural (sodium alginate, SA) polymer as film formers. Centrifugation and subsequent resuspension were employed to minimize residual solvent and increase drug loading (～20%) in the LAS suspensions and in the film. Film’s critical quality attributes (CQAs), including drug distribution and uniformity, mechanical properties, and dissolution were assessed. Crystalline nature of FNB was largely preserved in the film without any polymorphic changes confirmed by XRD, DSC, and Raman. The NIR chemical imaging, corroborated by SEM imaging and drug content relative standard deviation (RSD) indicates that the drug is uniformly distributed without any observable large agglomerates. The films with SA showed lower mechanical strength as compared to HPMC due to SA’s low molecular weight. All films exhibited immediate drug release as has been the case using FNB nano particles in previous papers. Interestingly, although addition of plasticizer improved film dissolution, HPMC-based films had a faster dissolution compared to SA-based films in spite of higher mechanical strength of the former.     

Evaluation and Controlled Release Characteristics of Modified Xanthan Films for Transdermal Delivery of Atenolol

ABSTRACT

The present study was performed to evaluate the possibility of using modified xanthan films as a matrix system for transdermal delivery of atenolol (ATL), which is an antihypertensive drug. Acrylamide was grafted onto xanthan gum (XG) by free radical polymerization using ceric ion as an initiator. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated the formation of the graft copolymer. The obtained graft copolymer was loaded with ATL and films were fabricated by solution casting method for transdermal application. Various formulations were prepared by varying the grafting ratio, drug loading, and different penetration enhancers. The formulations prepared were characterized for weight, thickness uniformity, water vapor transmission rate, and uniformity in drug content of the matrix. All the thin films were slightly opaque, smooth, flexible, and permeable to water vapor, indicating their permeability characteristics suitable for transdermal studies. Fourier transform infrared spectroscopy and differential scanning calorimetry studies indicated no significant interactions between drug and polymer. Drug is distributed uniformly in the matrix but showed a slight amorphous nature. Drug-loaded films were analyzed by X-ray diffraction to understand the drug polymorphism inside the films. Scanning electron microscopic studies of the placebo and drug-loaded films demonstrated a remarkable change in their surface morphology. The skin irritation tests were performed in mice and these results suggested that both placebo and drug-loaded films produced negligible erythema and edema compared to formalin (0.8% v/v) as the standard irritant. The in vitro drug release studies were performed in phosphate buffer saline using a Keshary-Chien diffusion cell. Different formulations were prepared and variations in drug release profiles were observed. Release data were analyzed by using the Ritger and Peppas equation to understand the mechanism of drug release as well as the estimation of n values, which ranged between 0.41 and 0.53, suggesting a Fickian diffusion trend.     

Diclofenac fast-dissolving film: suppression of bitterness by a taste-sensing system

Context: The selection of a proper taste-masking agent (TMA) is a critical issue in the development of fast‐dissolving films containing bitter drugs. Objective: This work is aimed to evaluate the suppression of the bitter taste of a maltodextrin fast-dissolving film loaded with 13.4 mg sodium diclofenac (DS) by adding TMAs. Methods: The films were prepared by casting and drying aqueous mixtures of maltodextrin (DE = 6), glycerin, sorbitan oleate, and DS. Films were characterized in terms of thickness, tensile properties, film disintegration time, and drug dissolution time. The bitterness intensity of DS and the masking effect of TMAs were evaluated by an electronic tongue. Results: The ‘mint’ and ‘licorice’ flavors and sucralose mixture resulted appropriate to mask DS bitterness as confirmed by a panel of volunteers. The addition of these TMAs did not significantly affect the film disintegration time (15–20 seconds) and DS dissolution rate (about 5 minutes). Conclusion: The electronic tongue was allowed to discriminate the effect of the TMA also in the presence of other hydrosoluble constituents of the film. Therefore, because of its simplicity and rapidity, this technique could assist or even replace the sensory evaluation in the development of fast‐dissolving films.     

Incorporation of paclitaxel solid dispersions with poloxamer188 or polyethylene glycol to tune drug release from poly(ϵ-caprolactone) films

Here we report the application of solid dispersion (SD) technique to improve paclitaxel (PTX) release from poly(?-caprolactone) (PCL)-based film. Paclitaxel solid dispersions (SDs) with either poloxamer188 (PXM) or polyethylene glycol (PEG) were successfully prepared by a melting method and then incorporated into PCL films, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and In vitro drug release/dissolution studies. It was found that PTX was faster released from the SDs than the corresponding physical mixtures (PMs) or PTX alone. For the PCL films with almost the same PTX loading, drug release from films containing SDs was remarkably faster than that from the film directly incorporated with PTX particles, and the films containing SDs with PXM exhibited a faster drug release than those with PEG. An increase In the content of PXM had no significant influence on PTX release from the films containing SDs. Incorporation of a higher content of SDs led to slower drug release from PCL films, indicating that PTX loading had a dominating effect on drug release. Through this study, we demonstrated the feasibility of the application of SD technique on the improvement of PTX release from PCL films and offered some beneficial information on modulating drug release behavior by changing the compositions and contents of the SDs-loaded PCL films.     

Study on poly(vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system

The distinguishable films composed of poly(vinyl alcohol) (PVA) and carboxymethyl-chitosan (CMCS) were prepared by blending/casting method, and loaded with ornidazole (OD) as local drug delivery system. In vitro test, the blend films showed pH-responsive swelling behavior and moderate drug release action, and also exhibited a little antimicrobial activity against E. coli and S. aureus strains. Those characteristics of CMCS/PVA blend films were essentially governed by the weight ratio of CMCS and PVA. Increasing the content of PVA in blend film would decrease swelling and decelerated the drug release. However, increasing the content of CMCS would enhance the antimicrobial activity. The biocompatibility and bioactivity of the blend film were also evaluated using rabbit blood and Wister rats. This blend drug system was of no hemolysis, no toxicity to rat periodontia and no cytotoxicity to the rat muscle. After subcutaneously implanting the blend drug films in Wister rat, the systems kept a good retention at the application site and maintained high drug concentration in long time (5 days) which was longer than the period of drug released in vitro (160 min).     

Valuation of a Cellulose Acetate (CA) latex as coating material for controlled release products

Cellulose acetate (CA) latex plasticized with 150% triacetin (TA) and 120% triethylcitrate (TEC), based on polymer weight, provided dense and homogeneous films when deposited onto propranolol HCl tablets using conventional fluid bed technology. Film permeability to the drug was low and flux/permeability enhancers were added to the CA structure during its manufacture. Films containing 40% surcrose and 10% PEG 8000 were found to provide the best release characteristics in terms of small lagtime (1 hour) and drug release profile (over 12 hours). When sucrose was added to TA or TEC plasticized fimls, a macroporous membrane was created during exposure to the dissolution fluid due to sucrose release from the film. These observations are consistent with the controlled porosity walls previously described for CA films deposited from organic solvents. It was postulated that drug mass transport occurs mainly within the porous CA structure and the mechanism responsible for its is a combination of molecular diffusion/osmotic pressure via water transport into the porous cellulose acetate membrane. Plasticizer loss during drying had also been demonstrated and related to the change in release profile seen with drying time.     

Development,optimization and evaluation of curcumin loaded biodegradable crosslinked gelatin film for the effective treatment of periodontitis

Objective: Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis.

Significance: Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis.

Methods: The film was developed by using solvent casting technique and “Design of Experiments” approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior.

Results: Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04?±?2.4, swelling index 138.10?±?1.25, and folding endurance 270?±?3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7?days.

Conclusions: The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.     

Evaluation of the film-forming property of hydrogenated rosin

The film-forming and coating properties of a new biomaterial, hydrogenated rosin (HR), is investigated in the present communication. Films produced by casting method are studied for mechanical, (tensile strength, elongation, and Young's modulus), water vapor transmission, and moisture absorption characteristics. Type of plasticizer and its concentration were observed to play an important role in modifying the film characteristics. Dibutyl sebacate (DBS), a hydrophobic plasticizer, was found to be suitable for development of flexible and smooth films. Film formulations plasticized with DBS were investigated for coating the drug layered nonpareil seeds where plasticization facilitated development of smooth and uniformly coated pellets. The increase in coat buildup, however, did not sustain the drug release significantly. The studies conclude that HR films promise utility as moisture-protective hydrophobic, film-coating materials.     

Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol

Background: Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application. Aim: Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion. Method: Interaction between atenolol and randomly methylated β-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release. Results: The formation of a stabile inclusion complex (K_s = 783.4?±?21.6 M^?1) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis. Conclusion: Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery.     

Valuation of a Cellulose Acetate (CA) latex as coating material for controlled release products

Abstract

Cellulose acetate (CA) latex plasticized with 150% triacetin (TA) and 120% triethylcitrate (TEC), based on polymer weight, provided dense and homogeneous films when deposited onto propranolol HCl tablets using conventional fluid bed technology. Film permeability to the drug was low and flux/permeability enhancers were added to the CA structure during its manufacture. Films containing 40% surcrose and 10% PEG 8000 were found to provide the best release characteristics in terms of small lagtime (1 hour) and drug release profile (over 12 hours). When sucrose was added to TA or TEC plasticized fimls, a macroporous membrane was created during exposure to the dissolution fluid due to sucrose release from the film. These observations are consistent with the controlled porosity walls previously described for CA films deposited from organic solvents. It was postulated that drug mass transport occurs mainly within the porous CA structure and the mechanism responsible for its is a combination of molecular diffusion/osmotic pressure via water transport into the porous cellulose acetate membrane. Plasticizer loss during drying had also been demonstrated and related to the change in release profile seen with drying time.     

Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy

Objective: The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone.

Materials and methods: A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application.

Results and discussion: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8?min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation.

Conclusions: HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.     

Preparation and Evaluation of Directly-Compressed Indomethacin, Indomethacin Sodium and Indomethacin Meglumine Tablets

A formula containing Compactrol, Ac-Di-Sol, Aerosil 200 and talc was used to prepare directly-compressed tablets of indomethacin and its sodium and meglumine salts. The prepared tablets were evaluated for uniformity of weight and thickness, hardness, friability and content uniformity. Each batch was then divided into two, one was coated with an opaque non-enteric film coat and evaluated for coat thickness uniformity. The dissolution rates of the uncoated and coated tablets and the effect of shelf-storage, at room temperature for 11 months, on drug contents were also studied. Indomethacin meglumine tablets showed the least relative standard deviation of weight and thickness. They exhibited acceptable uniformity of content and coat thickness, and the highest hardness-friability ratio. Also exhibited, uncoated and coated, the best in-vitro release of its drug contents and the maximal stability.     

Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment

Abstract

Introduction: Periodontal disease broadly defines group of conditions in which the supportive structure of the tooth (periodontium) is destroyed. Recent studies suggested that the anti-diabetic drug metformin hydrochloride (MF) has an osteogenic effect and is beneficial for the management of periodontitis.

Objective: Development of strong mucoadhesive multiple layer film loading small dose of MF for intra-pocket application.

Methodology: Multiple layer film was developed by double casting followed by compression method. Either 6% carboxy methyl cellulose sodium (CMC) or sodium alginate (ALG) constituted the inner drug (0.6%) loaded layer. Thiolated sodium alginate (TSA; 2 or 4%) constituted the outer drug free layers to enhance mucoadhesion and achieve controlled drug release. Optimized formulation was assessed clinically on 20 subjects.

Results: Films were uniform, thin and hard enough for easy insertion into periodontal pockets. Based on water uptake and in vitro drug release, CMC based film with 4% TSA as an outer layer was the optimized formulation with enhanced mucoadhesion and controlled drug release (83.73% over 12?h). SEM showed the effective fabrication of the triple layer film in which connective lines between the layers could be observed. FTIR examination suggests possibility of hydrogen bonding between the –NH groups of metformin and –OH groups of CMC. DSC revealed the presence of MF mainly in the amorphous form. Clinical results indicated improvement of all clinical parameters six months post treatment.

Conclusion: The results suggested that local application of the mucoadhesive multiple layer films loaded with metformin hydrochloride was able to manage moderate chronic periodontitis.     

Preparation and Evaluation of Directly-Compressed Indomethacin,Indomethacin Sodium and Indomethacin Meglumine Tablets

Abstract

A formula containing Compactrol, Ac-Di-Sol, Aerosil 200 and talc was used to prepare directly-compressed tablets of indomethacin and its sodium and meglumine salts. The prepared tablets were evaluated for uniformity of weight and thickness, hardness, friability and content uniformity. Each batch was then divided into two, one was coated with an opaque non-enteric film coat and evaluated for coat thickness uniformity. The dissolution rates of the uncoated and coated tablets and the effect of shelf-storage, at room temperature for 11 months, on drug contents were also studied. Indomethacin meglumine tablets showed the least relative standard deviation of weight and thickness. They exhibited acceptable uniformity of content and coat thickness, and the highest hardness-friability ratio. Also exhibited, uncoated and coated, the best in-vitro release of its drug contents and the maximal stability.