Fabrication and Characterization of Pectin Films Containing Solid Lipid Nanoparticles for Buccal Delivery of Fluconazole.

Fluconazole (FZ) is a potential antifungal compound for treating superficial and systemic candidiasis. However, the use of conventional oral drug products has some limitations. The development of buccal film may be a potential alternative to oral formulations for FZ delivery. The present study involved the development of novel FZ-loaded solid lipid nanoparticles (FZ-SLNs) in pectin solutions and the investigation of their particle characteristics. The particle sizes of the obtained FZ-SLNs were in the nanoscale range. To produce pectin films with FZ-SLNs, four formulations were selected based on the small particle size of FZ-SLNs and their suitable polydispersity index. The mean particle sizes of all chosen FZ-SLNs formulations did not exceed 131.7 nm, and the mean polydispersity index of each formulation was less than 0.5. The properties of films containing FZ-SLNs were then assessed. The preparation of all FZ-SLN-loaded pectin films provided the mucoadhesive matrices. The evaluation of mechanical properties unveiled the influence of particle size variation in FZ-SLNs on the integrity of the film. The Fourier-transform infrared spectra indicated that hydrogen bonds could potentially form between the pectin-based matrix and the constituents of FZ-SLNs. The differential scanning calorimetry thermogram of each pectin film with FZ-SLNs revealed that the formulation was thermally stable and behaved in a solid state at 37 °C. According to a drug release study, a sustained drug release pattern with a burst in the initial stage for all films may be advantageous for reducing the lag period of drug release. All prepared films with FZ-SLNs provided a sustained release of FZ over 6 h. The films containing FZ-SLNs with a small particle size provided good permeability across the porcine mucosa. All film samples demonstrated antifungal properties. These results suggest the potential utility of pectin films incorporating FZ-SLNs for buccal administration.

Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design.

The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X1), soybean oil (X2), and Tween 80 (X3) were used as solid lipid, liquid lipid, and stabilizer, respectively. The particle size of TA-loaded NLCs was lower than 200 nm and the zeta potential displayed the negative charge in all formulations. The percentage encapsulation efficiency (%EE) of the TA-loaded NLCs showed that it was higher than 80% for all formulations. Field emission scanning electron microscope (FESEM) confirmed that the size of TA-loaded NLCs was approximately 100 nm and energy-dispersive X-ray spectroscopy (EDS) confirmed that the TA could be incorporated in the NLC system. The Higuchi model gave the highest value of the R², indicating that this model was a fit for the TA release profiles of TA-loaded NLCs. Confocal laser scanning microscopy (CLSM) was used to observe the drug penetration within the porcine buccal mucosa and Nile red-loaded NLCs showed significantly higher penetration depth at 8 h than at 2 h. Therefore, TA-loaded NLCs could be an efficient carrier for drug delivery through the buccal mucosa.

Preparation and Characterization of Hydroxypropyl Methylcellulose/Polycarbophil Mucoadhesive Blend Films Using a Mixture Design Approach.

The objectives of this study were to prepare the hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend film and to investigate the main and interaction effect of HPMC and PC mixtures on the physicochemical and mechanical properties of blend films using a simplex lattice mixture design approach. The cubic and quadratic models were selected to analyze mucoadhesive properties in terms of work of adhesion and maximum detachment force, respectively. It was shown that HPMC/PC blend film had higher mucoadhesive properties than pure HPMC film. The suitable models for analyzing swelling index of blend films at various times were assessed. The puncture strength, % elongation and hydrophilicity of films were also examined. The pure HPMC film displayed more homogeneous and smoother structures compared with the blend film, as observed by scanning electron microscope and atomic force microscopy. Intermolecular hydrogen bonding between HPMC and PC was detected using Fourier transform infrared and X-ray diffraction. Therefore, the blend film shows high potential for use as a buccal delivery system.

Effect of Cremophor RH40, Hydroxypropyl Methylcellulose, and Mixing Speed on Physicochemical Properties of Films Containing Nanostructured Lipid Carriers Loaded with Furosemide Using the Box-Behnken Design.

This study aimed to examine the characteristics of H-K4M hydroxypropyl methylcellulose (HPMC) films containing nanostructured lipid carriers (NLCs) loaded with furosemide. A hot homogenization technique and an ultrasonic probe were used to prepare and reduce the size of the NLCs. Films were made using the casting technique. This study used a Box-Behnken design to evaluate the influence of three key independent variables, specifically H-K4M concentration (X1), surfactant Cremophor RH40 concentration (X2), and mixing speed (X3), on the physicochemical properties of furosemide-loaded NLCs and films. The furosemide-loaded NLCs had a particle size ranging from 54.67 to 99.13 nm, and a polydispersity index (PDI) ranging from 0.246 to 0.670. All formulations exhibited a negative zeta potential, ranging from -7.05 to -5.61 mV. The prepared films had thicknesses and weights ranging from 0.1240 to 0.2034 mm and 0.0283 to 0.0450 g, respectively. The drug content was over 85%. Film surface wettability was assessed based on the contact angle, ranging from 32.27 to 68.94°. Film tensile strength varied from 1.38 to 7.77 MPa, and their elongation at break varied from 124.19 to 170.72%. The ATR-FTIR analysis confirmed the complete incorporation of the drug in the film matrix. Therefore, the appropriate selection of values for key parameters in the synthesis of HPMC films containing drug-loaded NLCs is important in the effective development of films for medical applications.

Nanoparticle formation by using shellac and chitosan for a protein delivery system.

The potential of using two natural polymers (chitosan and shellac) for the formation of nanoparticles by the process of ionic cross-linking to encapsulate bovine serum albumin, a model protein was investigated. Depending on the concentrations of chitosan, shellac and bovine serum albumin, three physical states - nanoparticle, aggregation, and solution could be observed as a result of the electrostatic force. The formation of nanoparticles was due to the balance between the repulsion force and attractive force while the imbalance between both forces resulted in the formation of aggregation and solution. The Fourier transform infrared spectroscopy and differential scanning calorimetry were applied to prove the nanoparticle formation. The particle size was characterized by the light scattering technique and was found in the range between 100 and 300 nm. The morphology of the particles, detected by transmission electron microscopy was spherical shape. The result showed that the zeta potential of the nanoparticles possessed positive charges. The concentrations of chitosan, shellac and bovine serum albumin had an influence on the physicochemical properties of the nanoparticles such as the particle size, the zeta potential, the encapsulation, the loading efficiencies and the cumulative release. Therefore, chitosan and shellac could be used to form nanoparticles for protein delivery by the ionic cross-linking method.

Role of Bovine Serum Albumin Addition in Micellization and Gel Formation of Poloxamer 407.

The combination of the thermoresponsive polymer and protein has demonstrated great promise in its applications in drug delivery and tissue engineering fields. This study described the impact of bovine serum albumin (BSA) on the micellization and sol-gel transition behaviors of poloxamer 407 (PX). The micellization of aqueous PX solutions with and without BSA was examined using isothermal titration calorimetry. In the calorimetric titration curves, the pre-micellar region, the transition concentration region, and the post-micellar region were observed. The presence of BSA had no noticeable impact on critical micellization concentration, but the inclusion of BSA caused the pre-micellar region to expand. In addition to studying the self-organization of PX at a particular temperature, the temperature-induced micellization and gelation of PX were also explored using differential scanning calorimetry and rheology. The incorporation of BSA had no discernible effect on critical micellization temperature (CMT), but it did affect gelation temperature (Tgel) and gel integrity of PX-based systems. The response surface approach illustrated the linear relation between the compositions and the CMT. The major factor affecting the CMT of the mixtures was the concentration of PX. The alteration of the Tgel and the gel integrity were discovered to be a consequence of the intricate interaction between PX and BSA. BSA mitigated the inter-micellar entanglements. Hence, the addition of BSA demonstrated a modulating influence on Tgel and a softening effect on gel integrity. Understanding the influence of serum albumin on the self-assembly and gelation of PX will enable the creation of thermoresponsive drug delivery and tissue engineering systems with controlled gelation temperatures and gel strength.

Curcumin-loaded methacrylate pullulan with grafted carboxymethyl-ß-cyclodextrin to form hydrogels for wound healing: In vitro evaluation.

A pullulan (Pul)-derivative hydrogel was developed by introducing methacrylate (MA) groups and ß-cyclodextrin (ßCD) to form a Pul-ßCD-MA hydrogel by UV cross-linking. The MA was expected to improve the hydrogel's mechanical properties and the ßCD to increase the solubility of curcumin. Pul-ßCD-MA was successfully synthesized, as confirmed by the 1H NMR and FTIR spectra. Hydrogels were formed at Pul-ßCD-MA concentrations of 5 %, 7.5 %, or 10 % w/v. Pul-ßCD-MA showed enhanced curcumin solubility compared to Pul or Pul-MA. The morphological analysis of the hydrogel showed a porous structure. The concentration of ßCD affected the hydrogels' mechanical properties, and the 7.5 % hydrogel (with or without curcumin) did not fracture. The cumulative release of curcumin in the 7.5 % Pul-ßCD-MA hydrogel was 60 % over 8 h. The release profile fit the Korsmeyer-Peppas model. In vitro cytotoxicity tests revealed that hydrogels were biocompatible with human primary dermal fibroblast cells. Curcumin-loaded Pul-ßCD-MA hydrogels significantly accelerated wound healing compared to Pul-ßCD-MA hydrogels without curcumin loading. Therefore, the Pul derivative's hydrogel may be a promising material for wound healing.

Drug-Polymers Composite Matrix Tablets: Effect of Hydroxypropyl Methylcellulose (HPMC) K-Series on Porosity, Compatibility, and Release Behavior of the Tablet Containing a BCS Class I Drug.

The purpose of this research was to see how the physicochemical properties and porosity of matrix tablets containing various types of hydroxypropyl methylcellulose (HPMC) K series affected the release of propranolol hydrochloride (PNL). PNL is a class I drug (high solubility and permeability) according to the Biopharmaceutics Classification System (BCS), making it an excellent model drug used for studying extended-release drug products. The direct compression method was used to prepare the HPMC-based matrix tablets. PNL and the excipients were found to be compatible using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The surfaces of all the compressed HPMC-based matrix tablets were rough, with accumulated particles and small holes. The compressed HPMC-based matrix tablet porosity was also determined by using mercury porosimetry. The compressed HPMC-based matrix tablets made of low viscosity HPMC had tiny pores (diameter < 0.01 µm). The shorter polymeric chains are more prone to deformation, resulting in a small pore proportion. The compressed HPMC-based matrix tablets sustained the release of PNL for over 12 h. The release exponent values (n), which reflect the release mechanism of the drug from the tablets, ranged from 0.476 to 0.497. These values indicated that the release was governed by anomalous transport. The compressed HPMC-based matrix tablets have the potential for a sustained release of PNL.

Design and development of 3D-printed bento box model for controlled drug release of propranolol HCl following pharmacopeia dissolution guidelines.

The goal of this study was to develop a 3D-printed bento box model (3D-printed BB) with one or two chambers containing propranolol hydrochloride (PNL) as powder and matrix tablet for controlled drug release at varying times using United States Pharmacopeia (USP) dissolution guidelines. The 3D-printed BBs were made with commercial polyvinyl alcohol filament and a fused deposition modeling (FDM) 3D printer, with varying infill percentages and wall thicknesses. The physicochemical properties of the 3D-printed BBs, including appearance, thickness, size, weight, hardness, swelling, and erosion properties were investigated. The surface and cross-section morphologies of the 3D-printed BBs were characterized using a FESEM. According to FESEM images, the different infill percentages had a significant effect on the internal structure of the 3D-printed BBs' caps, but a minor effect on the internal structure of their walls. PNL release from the 3D-printed BB began in a pH 1.2 medium, followed by drug release in a pH 6.8 medium. Some formulations of 3D-printed BB could achieve a drug release percentage within all the ranges specified by USP dissolution guidelines. 3D-printed BBs, therefore, have the potential to revolutionize the future of the pharmaceutical industry by facilitating control of the amount of drugs released at predetermined intervals.

Thermosensitive Polymer Blend Composed of Poloxamer 407, Poloxamer 188 and Polycarbophil for the Use as Mucoadhesive In Situ Gel.

Herein, thermosensitive blends of poloxamer 407 (P407)/poloxamer 188 (P188)/polycarbophil (PCB) were developed in terms of maximized content of PCB (a mucoadhesive polymer) and desired temperature-dependent rheological properties of the blends as in situ gelling matrices. Maximizing PCB content while achieving the preferable rheological characteristics was accomplished through the Box-Behnken design. The quantitative effect of the polymer composition in the blends on the thermosensitive characteristics was evaluated using the fitted design model and the corresponding surface plots. The optimized P407/P188/PCB blend (OPT) was the mixture of 20.000, 7.349 and 0.595% (w/w) of P407, P188, and PCB, respectively. The thermosensitive micellization of OPT was investigated using differential scanning calorimetry which revealed an overlapping double endothermic peak caused by the temperature-induced micellization of pure micelles in co-existence with the micelles with attached PCB. Mixing PCB with the P407/P188 matrix promoted a more intense mucoadhesion of the blend. After incorporating metronidazole, a model hydrophilic drug, into OPT, the temperature-dependent characteristics of the hydrogel did not change. Metronidazole release from OPT was sustained by an anomalous mechanism. This optimal ternary hydrogel benefiting from thermosensitive gelling and mucoadhesive matrix might be used as a viable platform for mucoadhesive in situ gelling drug delivery.

Chitosan film containing antifungal agent-loaded SLNs for the treatment of candidiasis using a Box-Behnken design.

The aim of this study was to combine fluconazole (FZ)-loaded solid lipid nanoparticles (FZ-SLNs) and chitosan films (C-films) for the potential administration of FZ across the buccal mucosa using a Box-Behnken design. The chitosan films containing FZ-SLNs (C-FS-films) and C-films were prepared using a film casting method. The ATR-FTIR analysis confirmed the presence of hydrogen bonds between the NH3+ groups of chitosan and the OH or COO- groups of glyceryl monostearate in the films. Additionally, FESEM analysis of the morphology of C-FS-films revealed the presence of FZ-SLNs in the films. Permeation studies using porcine buccal mucosa demonstrated that FZ from the C-FS-films was more permeable than in C-films. The antifungal activity of the C-FS-films was evaluated against Candida albicans, and inhibition zones were observed. Thus, C-FS-films represent an exciting drug carrier for the treatment of candidiasis via the buccal mucosa.

Optimization of orodispersible and conventional tablets using simplex lattice design: Relationship among excipients and banana extract.

The objective of this study was focused on the optimization of the pharmaceutical excipients and banana extract in the preparation of orally disintegrating banana extract tablets (OD-BET) and conventional banana extract tablets (CO-BET) using a simplex lattice design. Various ratios of banana extract (BE), dibasic calcium phosphate (DCP) and microcrystalline cellulose (MCC) were used to prepare banana extract tablets (BET). The results indicated that the optimal OD-BET and CO-BET consisted of BE: DCP: MCC at 10.0, 88.8, 1.2, 10.0, 83.8: and 6.2, respectively. AFM demonstrated that the surface of BET with BE + MCC was smooth and compacted when compared to BET with BE + DCP + MCC and BE + DCP. FTIR and XRD showed a correlation in the results and indicated that no interaction of each ingredient occurred in the process of BET formulation. Therefore, the experimental design is potentially useful in formulated OD-BET and CO-BET by using only one design simultaneously.

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles.

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10-20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10-30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.