Search Results (35)

Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In this study, we aimed to develop and characterize CPC-Mont-containing coating films for dentures, focusing on their physicochemical behaviors and antifungal efficacies. Methods: CPC was intercalated into sodium-type montmorillonite to prepare CPC-Mont; thereafter, films containing CPC-Mont were fabricated using emulsions of different polymer types (nonionic, cationic, and anionic). CPC loading, release, and recharging behaviors were assessed at various temperatures, and activation energies were calculated using Arrhenius plots. Antimicrobial efficacy against Candida albicans was evaluated for each film using standard microbial assays. Results: X-ray diffraction analysis confirmed the expansion of montmorillonite interlayer spacing by approximately 3 nm upon CPC loading. CPC-Mont showed temperature-dependent release and recharging behavior, with higher temperatures enhancing its performance. The activation energy for CPC release was 38 kJ/mol, while that for recharging was 26 kJ/mol. Nonionic emulsions supported uniform CPC-Mont dispersion and successful film formation, while cationic and anionic emulsions did not. CPC-Mont-containing coatings maintained antimicrobial activity against Candida albicans on dentures. Conclusions: CPC-Mont can be effectively incorporated into nonionic emulsion-based films to create antimicrobial coatings for denture applications. The films exhibited temperature-responsive, reversible CPC release and recharging behaviors, while maintaining antifungal efficacy, findings which suggest the potential utility of CPC-Mont-containing films as a practical strategy to prevent denture-related candidiasis. Full article

Due to advances in edible films based on polysaccharides that can carry an active pharmaceutical ingredient (API), these films now provide rapid and effective release upon consumption. These films provide an alternative to conventional drug delivery methods and are known as orally disintegrating films (ODFs). This study aimed to evaluate the capacity of an edible film composed of starch, chitosan, and maltodextrin to carry an API while maintaining its physicochemical and surface properties. Acetaminophen, a hydrophilic drug, was selected as the model API and incorporated into the edible film. The film achieved an API loading capacity of approximately 4.37 mg—comparable to the standard doses of certain hydrophilic drugs. Chemical analysis using vibrational spectroscopy revealed strong intermolecular interactions between the components. X-ray diffraction analysis confirmed these interactions through a decrease in crystallinity within the biopolymeric compounds, while the model API retained its structural ordering. However, water absorption values increased by approximately 90% in the edible film. Scanning electron microscopy images showed a homogeneous dispersion of the model API throughout the film, without aggregation, demonstrating that the film can effectively accommodate this drug concentration. Furthermore, the elasticity remained comparable in both formulations, with a Young’s modulus of 9.27 MPa for the control film and 9.38 MPa for the API-loaded film. Overall, the edible film developed in this study represents a promising system for API delivery. Full article

Background/Objectives: Drug–polymer interactions and miscibility promote the formation and performance of amorphous solid dispersions (ASDs) of poorly soluble drugs for improved oral bioavailability. The objective of this study was to employ drug–polymer interaction calculations and small-scale experimental characterization to screen polymers for potential ASDs of ritonavir. Methods: Seven polymers across four polymer types were screened as follows: an enteric one (EudragitS100), amphiphilic ones (HPMCAS-L, HPMCAS-H, and their 1:1 combination), hydrophilic ones (PEG-6000, PVP-VA), and a surfactant (Soluplus), including PVP-VA as a positive control, as the commercial ASD employs PVP-VA. Drug–polymer interaction calculations were performed for Hansen solubility parameter, Flory–Huggins parameter, and glass transition temperature. ASDs were prepared via film casting. Experimental characterizations included drug solubility in polymer solutions, polymer inhibition of drug precipitation, polarized light microscopy, differential scanning calorimetry, solubilization capacity, and dissolution studies. Results: HPMCAS-L, HPMCAS L:H, and Soluplus, along with the positive control PVP-VA, were identified as polymers for potential ASDs of ritonavir, with HPMCAS-L and PVP-VA being preferable. HPMCAS-L and the positive control PVP-VA were always viable for both 20% and 40% drug loads across all tests. Films with each of these four polymers showed improved dissolution compared to amorphous ritonavir without polymer. Drug–polymer interaction calculations anticipated the unfavorable small-scale experimental results for PEG-6000 and EudragitS100. Conclusion: Overall, the results contribute towards a resource-sparing approach to identify polymers for ASDs. Full article

This study aims to evaluate the adsorptive, adhesive, and wetting energetic properties of five commercially available cleansers in contact with model dental polymer (PMMA). It was assumed that the selected parameters allow for determining the optimal concentration and place of key component accumulation for antibacterial activity in the bulk liquid phase and prevention of oral plaque formation at the prosthetic material surface. The adsorptive (Gibbs’ excesses Γ_LV, critical micellar concentration) and thermal (entropy and enthalpy) surface characteristics originated from surface tension γ_LV(T) and γ_LV(C) dependences. The surface wetting properties were quantified upon the contact angle hysteresis formalism on the advancing Θ_A, receding Θ_R contact angles, and γ_LV as the input data, which yield a set of wettability parameters: 2D adsorptive film pressure, surface free energy with its dispersive and polar components, work of adhesion, and adhesional tension, considered as interfacial interaction indicators. In particular, molecular partitioning K_p and Γ_LV are indicators of the efficiency of particular active substance accumulation in the volume phase, while γ_SV, a = Γ_SL/Γ_LV, and W_A point to the degree of its accumulation at the immersed polymer surface. Finally, the liquid penetration coefficient PC and the Marangoni temperature gradient-driven liquid flow speed were estimated. Full article

Tadalafil (TD) has poor water solubility but is well absorbed without affecting food intake when administered orally. Owing to patient adherence and therapeutic characteristics, a TD-loaded orodispersible film (TDF) is preferable. However, the mechanistic role of dietary status on the clinical pharmacokinetic analysis of TDF in human volunteers should be investigated because the gastrointestinal environment varies periodically according to meal intervals, although commercial 20 mg TD-loaded tablets (TD-TAB, Cialis^® tablet) may be taken with or without food. TDF was prepared by dispersing TD in an aqueous solution and polyethylene glycol 400 to ensure good dispersibility of the TD particles. In the fasting state, each T/R of Cmax and AUC between TD-TAB and TDF showed bioequivalence with 0.936–1.105 and 1.012–1.153, respectively, and dissolution rates in 1000 mL water containing 0.5% SLS were equivalent. In contrast, TDF was not bioequivalent to TD-TAB under the fed conditions by the C_max T/R of 0.610–0.798. The increased dissolution rate of TDF via the micronization of drug particles and the reduced viscosity of the second meal content did not significantly affect the bioequivalence. Interestingly, an increase in second meal intake time from 4 h to 6 h resulted in the bioequivalence by the Cmax T/R of 0.851–0.998 of TD-TAB and TDF. The predictive diffusion direction model for physical digestion of TD-TAB and TDF in the stomach after the first and second meal intake was successfully simulated using computational fluid dynamics modeling, accounting for the delayed drug diffusion of TDF caused by prolonged digestion of stomach contents under postprandial conditions. Full article

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H₂ receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid^® 244FP and poloxamer^® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect. Full article

The current study aimed to fabricate curcumin-loaded bilosomal hydrogel for topical wound healing purposes, hence alleviating the poor aqueous solubility and low oral bioavailability of curcumin. Bilosomes were fabricated via the thin film hydration technique using cholesterol, Span^® 60, and two different types of bile salts (sodium deoxycholate or sodium cholate). Bilosomes were verified for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and in vitro drug release besides their morphological features. The optimum formulation was composed of cholesterol/Span^® 60 (molar ratio 1:10 w/w) and 5 mg of sodium deoxycholate. This optimum formulation was composed of a PS of 246.25 ± 11.85 nm, PDI of 0.339 ± 0.030, ZP of −36.75 ± 0.14 mv, EE% of 93.32% ± 0.40, and the highest percent of drug released over three days (96.23% ± 0.02). The optimum bilosomal formulation was loaded into alginate dialdehyde/chitosan hydrogel cross-linked with calcium chloride. The loaded hydrogel was tested for its water uptake capacity, in vitro drug release, and in vivo studies on male Albino rats. The results showed that the loaded hydrogel possessed a high-water uptake percent at the four-week time point (729.50% ± 43.13) before it started to disintegrate gradually; in addition, it showed sustained drug release for five days (≈100%). In vivo animal testing and histopathological studies supported the superiority of the curcumin-loaded bilosomal hydrogel in wound healing compared to the curcumin dispersion and plain hydrogel, where there was a complete wound closure attained after the three-week period with a proper healing mechanism. Finally, it was concluded that curcumin-loaded bilosomal hydrogel offered a robust, efficient, and user-friendly dosage form for wound healing. Full article

Curcumin’s ability to impact chronic inflammatory conditions, such as metabolic syndrome and arthritis, has been widely researched; however, its poor bioavailability limits its clinical application. The present study is focused on the development of curcumin-loaded polymeric nanomicelles as a drug delivery system with anti-inflammatory effects. Curcumin was loaded in PEG-60 hydrogenated castor oil and puronic F127 mixed nanomicelles (Cur-RH60/F127-MMs). Cur-RH60/F127-MMs was prepared using the thin film dispersion method. The morphology and releasing characteristics of nanomicelles were evaluated. The uptake and permeability of Cur-RH60/F127-MMs were investigated using RAW264.7 and Caco-2 cells, and their bioavailability and in vivo/vitro anti-inflammatory activity were also evaluated. The results showed that Cur-RH60/F127-MMs have regular sphericity, possess an average diameter smaller than 20 nm, and high encapsulation efficiency for curcumin (89.43%). Cur-RH60/F127-MMs significantly increased the cumulative release of curcumin in vitro and uptake by cells (p < 0.01). The oral bioavailability of Cur-RH60/F127-MMs was much higher than that of curcumin-active pharmaceutical ingredients (Cur-API) (about 9.24-fold). The treatment of cell lines with Cur-RH60/F127-MMs exerted a significantly stronger anti-inflammatory effect compared to Cur-API. In addition, Cur-RH60/F127-MMs significantly reduced OVA-induced airway hyperresponsiveness and inflammation in an in vivo experimental asthma model. In conclusion, this study reveals the possibility of formulating a new drug delivery system for curcumin, in particular nanosized micellar aqueous dispersion, which could be considered a perspective platform for the application of curcumin in inflammatory diseases of the airways. Full article

The main aims of thin biofilm synthesis are to either achieve a new form to promote the transport of drugs in oral delivery systems or as a coating to improve the biocompatibility of the implant’s surface. In this study, the Langmuir monolayer technique was employed to obtain films containing Mg-doped hydroxyapatite with 0.5%, 1.0%, and 1.5% Mg(II). The obtained modified HA particles were analysed via the FT-IR, XRD, DLS, and SEM methods. It was shown that the modified hydroxyapatite particles were able to form thin films at the air/water interface. BAM microscopy was employed to characterized the morphology of these films. In the next step, the mixed films were prepared using phospholipid (DPPC) molecules and modified hydroxyapatite particles (HA-Mg(II)). We expected that the presence of phospholipids (DPPC) in thin films improved the biocompatibility of the preparing films, while adding HA-Mg(II) particles will promote antibacterial properties and enhance osteogenesis processes. The films were prepared in two ways: (1) by mixing DPPC and HA-Mg (II) and spreading this solution onto the subphase, or (2) by forming DPPC films, dropping the HA-Mg (II) dispersion onto the phospholipid monolayer. Based on the obtained π–A isotherms, the surface parameters of the achieved thin films were estimated. It was observed that the HA-Mg(II) films can be stabilized with phospholipid molecules, and a more stable structure was obtained from films synthesied via method (2). Full article

Nisoldipine (NIS) is a calcium channel blocker that exhibits poor bioavailability (~5%) due to low aqueous solubility and presystemic metabolism in the gut wall. In this context, the present work aimed to develop NIS solid dispersion (NISSD)-based sublingual films using solvent casting technique to improve the dissolution. Phase solubility studies indicated that Soluplus^® was the most effective carrier for improving the aqueous solubility of NIS. NISSDs were initially developed using the solvent evaporation method. Fourier transform infrared spectrometric studies were found to display the characteristic vibrational bands related to C=O stretching and N-H deformation in NISSDs, proving the chemical integrity of the drug in NISSDs. Subsequently, bioadhesive sublingual films of NISSDs were formulated using solvent casting method, using hydroxypropyl methyl cellulose (HPMC) E5, E15, and hydroxy ethyl cellulose (HEC EF) as hydrophilic polymers and polyethylene glycol 400 (PEG 400) as plasticizer. The incorporation of NISSDs was found to produce clear films that displayed uniform content. The sublingual film of NISSDs composed of HPMC E5 (2% w/v), was found to display the least thickness (0.29 ± 0.02 mm), the highest folding endurance (168.66 ± 4.50 times), and good bioadhesion strength (12.73 ± 0.503 g/cm²). This film was found to rapidly disintegrate (28.66 ± 3.05 sec) and display near-complete drug release (94.24 ± 1.22) in 30 min. Incorporating NISSDs into rapidly bioadhesive sublingual films considerably improves drug dissolution. Overall, these research outcomes underscored the potential of rapidly dissolving bioadhesive sublingual films to evade gut metabolism and resolve the bioavailability issues associated with oral administration of NIS. Full article

The therapeutic effectiveness of paliperidone in the treatment of schizophrenia has been limited by its poor oral bioavailability; hence, an alternative route could be appropriate. This study investigates the feasibility of developing a buccal film impregnated with paliperidone-loaded nanostructured lipid carriers (NLCs) and assesses the potential to enhance its bioavailability. Box–Behnken-based design optimization of NLCs was performed by examining the particles’ physical characteristics. The polymeric film was used to load optimized NLCs, which were then assessed for their pharmaceutical properties, permeability, and pharmacokinetics. The optimization outcomes indicated that selected formulation variables had a considerable (p < 0.05) impact on responses such as particle size, entrapment efficiency, and % drug release. Desired characteristics such as a negative charge, higher entrapment efficiency, and nanoparticles with ideal size distribution were shown by optimized NLC dispersions. The developed film demonstrated excellent physico-mechanical properties, appropriate texture, good drug excipient compatibility (chemically stable formulation), and amorphous drug nature. A sustained Weibull model drug release (p < 0.0005) and superior flux (~5-fold higher, p < 0.005) were seen in NLC-loaded film compared to plain-drug-loaded film. The pharmacokinetics profile in rabbits supports the goal of buccal therapy as evidenced by significantly higher AUC_0–12 (p < 0.0001) and greater relative bioavailability (236%) than the control. These results support the conclusion that paliperidone-loaded NLC buccal film has the potential to be an alternate therapy for its effective administration in the treatment of schizophrenia. Full article

Hypertension can begin in childhood; elevated blood pressure in children is known as pediatric hypertension. Contrary to adult hypertension, there is a scarcity of commercial medications suitable for the treatment of pediatric hypertension. The aim of this study was to develop orally dispersible films (ODFs) loaded with captopril for the treatment of hypertension in children. Captopril-loaded ODFs were composed of different blends of synthetic polymers, such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone, and natural polymers, such as sodium alginate (SA) and gelatin. The ODFs were characterized based on their mechanical and thermal properties, drug content, surface morphology, in vitro disintegration, in vitro release, and bioavailability. A novel HPLC method with precolumn derivatization was developed to precisely and selectively determine captopril levels in plasma. A low concentration of PVA and a high concentration of SA generated ODFs with faster hydration and disintegration rates. SA-based films exhibited fast disintegration properties (1–2 min). The optimized modified-release film (F2) showed significant (p < 0.05) enhancement in bioavailability (AUC = 1000 ng min/mL), with a value 1.43 times that of Capoten^® tablets (701 ng min/mL). While the plasma concentration peaking was in favor of the immediate-release tablet, T_max was significantly prolonged by 5.4 times for the optimized ODF (3.59 h) compared with that of the tablets (0.66 h). These findings indicate uniform and sustained plasma concentrations, as opposed to the pulsatile and rapid plasma peaking of captopril from the immediate-release tablets. These findings suggest that the modified release of oral films could offer more favorable plasma profiles and better control of hypertension than the conventional release tablets. Full article

Chitosan (CS) films exhibit great potential as a substrate for the in vitro mineralization process. In this study, to mimic the formation of nanohydroxyapatite (HAP) as natural tissue, CS films coated with a porous calcium phosphate were investigated using scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), Fourier transforms infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). Calcium phosphate coating deposited on phosphorylated derivatives of CS was obtained by a process based on phosphorylation, Ca(OH)₂ treatment and artificial saliva solution (ASS) immersion. The phosphorylated CS films (PCS) were obtained by partial hydrolysis of the PO₄ functionalities. It was demonstrated that this precursor phase could induce the growth and the nucleation of the porous calcium phosphate coating when immersed in ASS. Moreover, oriented crystals and qualitative control of calcium phosphate phases on CS matrices are obtained in a biomimetic mode. Furthermore, in vitro antimicrobial activity of PCS was evaluated against three species of oral bacteria and fungi. It revealed an increase in antimicrobial activity with minimum inhibition concentration (MIC) values of 0.10% (Candida albicans), 0.05% (Staphylococcus aureus) and 0.025% (Escherichia coli) which proves their possible use as dental substitute materials. Full article

Curcumin, a polyphenolic extract from the rhizomes of turmeric, exhibits antioxidant, anti-inflammatory, and anticancer activities, which are beneficial for the treatment of gastric diseases. However, curcumin’s therapeutic usefulness is restricted by its low aqueous solubility and short gastric residence time. In this study, curcumin-loaded solid dispersion (ratio 1:5) was prepared using Eudragit^® EPO (Cur EPO-SD), resulting in an approximately 12,000-fold increase in solubility to 6.38 mg/mL. Expandable films incorporating Cur EPO-SD were subsequently prepared by solvent casting using different types of starch (banana, corn, pregelatinized, and mung bean starch) in combination with chitosan. Films produced from banana, corn, pregelatinized and mung bean starch unfolded and expanded upon exposure to simulated gastric medium, resulting in sustained release of 80% of the curcumin content within 8 h, whereas films based on pregelatinized starch showed immediate release characteristics. Curcumin-loaded expandable films based on different types of starch exhibited similar cytotoxic effects toward AGS cells and more activity than unformulated curcumin. Furthermore, the films resulted in increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate the potential of expandable curcumin-loaded films as gastroretentive dosage forms for the treatment of gastric diseases and to improve oral bioavailability. Full article

Luteolin (LUT), a bioactive flavonoid, possesses various pharmacological properties, including antioxidant, antimicrobial, anti-allergic, cardio-protective, and anti-cancer activity. Among them, LUT’s administration for the treatment of periodontal disease is very promising. However, its low water solubility magnifies the challenge of formulating LUT into an effective dosage form. In this vein, the aim of the present study examines the preparation of amorphous solid dispersions (ASD) for the solubility improvement of LUT in saliva. At first, the physicochemical properties of the active pharmaceutical ingredient (API) were studied before the selection of the most suitable ASD matrix/carrier. For this reason, six commonly used polymeric ASD matrix/carriers (namely, povidone, PVP; copovidone, coPVP; hydroxypropyl cellulose, HPC-SL; hydroxypropyl methyl cellulose acetate succinate, HPMC-AS; Eudragit^® RS, Eud-RS; and Soluplus^®, SOL) were screened via the film casting method, as to whether they could suspend the drug’s recrystallization. The most promising matrix/carriers were then evaluated, based on their ability to inhibit LUT’s precipitation after its solubilization, via the solvent shift method. Based on both screening methods, it was determined that PVP was the most promising matrix/carrier for the preparation of LUT’s ASDs. Hence, in a further step, after the successful testing of components’ miscibility, LUT-PVP ASDs were prepared via the solvent evaporation method. These systems (examined via powder X-ray diffractometry, pXRD) showed full API amorphization immediately after preparation and excellent physical stability (since they were stable after 3 months of storage). The study of LUT-PVP ASD’s ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared) spectra demonstrated strong H-bonds between the molecules of the drug and the matrix/carrier, while molecular dynamics (MD) simulations were able to shed light on these drug–matrix/carrier interactions, at a molecular level. Finally, in vitro dissolution studies in simulated saliva proved that the prepared ASDs were able to significantly enhance LUT’s dissolution profile. Hence, according to findings of the present work, the preparation of LUT-ASDs utilizing PVP as the polymeric matrix/carrier is regarded as a highly promising technique for the improvement of API’s solubility in the oral cavity. Full article