QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T _60%?>?6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T _max, K _a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.     

Formulation and <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4?×?2² factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X ₁), drug–lipid ratio (X ₂), and filler type (X ₃) on the percentage drug released at 8, 12, and 24 h (Y ₁, Y ₂, and Y ₃) as dependent variables. Sixteen TBS sustained-release matrices (F1–F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug–Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.     

Colon-Targeted Delivery of IgY Against <Emphasis Type="Italic">Clostridium difficile</Emphasis> Toxin A and B by Encapsulation in Chitosan-Ca Pectinate Microbeads

This study investigated the use of a newly developed chitosan-Ca pectinate microbead formulation for the colon-targeted delivery of anti-A/B toxin immunoglobulin of egg yolk (IgY) to inhibit toxin binding to colon mucosa cells. The effect of the three components (pectinate, calcium chloride, and chitosan) used for the microbead production was examined with the aim of identifying the optimal levels to improve drug encapsulation efficiency, swelling ratio, and cumulative IgY release rate. The optimized IgY-loaded bead component was pectin 5% (w/v), CaCl₂ 3% (w/v), and chitosan 0.5% (w/v). Formulated beads were spherical with 1.2-mm diameter, and the drug loading was 45%. An in vitro release study revealed that chitosan-Ca pectinate microbeads inhibited IgY release in the upper gastrointestinal tract and significantly improved the site-specific release of IgY in the colon. An in vivo rat study demonstrated that 72.6% of biologically active IgY was released specifically in the colon. These results demonstrated that anti-A/B toxin IgY-loaded chitosan-Ca pectinate oral microbeads improved IgY release behavior in vivo, which could be used as an effective oral delivery platform for the biological treatment of Clostridium difficile infection (CDI).     

Design and Evaluation of Hydrophilic Matrix System Containing Polyethylene Oxides for the Zero-Order Controlled Delivery of Water-Insoluble Drugs

The aim of this study was to design a polyethylene oxide (PEO) binary hydrophilic matrix controlled system and investigate the most important influence(s) on the in vitro water-insoluble drug release behavior of this controlled system. Direct-compressed PEO binary matrix tablets were obtained from a variety of low viscosity hydrophilic materials as a sustained agent, using anhydrous drugs as a model drug. Water uptake rate, swelling rate, and erosion rate of matrices were investigated for the evaluation of the PEO hydrophilic matrix systems. The effect of the dose, the solubility of water-insoluble drug, and the rheology of polymers on in vitro release were also discussed. Based on the in vitro release kinetics study, three optimized PEO binary matrices were selected for further research. And, these PEO binary matrices had shown the similar release behavior that had been evaluated by the similarity factor f ₂. Further study indicated that they had identical hydration, swelling, and erosion rate. Moreover, rheology study exhibited the similar rheological equation of Herschel–Bulkley and their viscosity was also within the same magnitude. Therefore, viscosity plays the most important role to control drug release compared to other factors in PEO binary matrix system. This research provides fundamental understanding of in vitro drug release of PEO binary hydrophilic matrix tablets and helps pharmaceutical workers to develop a hydrophilic controlled system, which will effectively shorten the process of formulation development by reducing trial-and-error.     

Pharmacokinetic Evaluation of Improved Oral Bioavailability of Valsartan: Proliposomes <Emphasis Type="Italic">Versus</Emphasis> Self-Nanoemulsifying Drug Delivery System

The objective of this study was to develop proliposomes and self-nanoemulsifying drug delivery system (SNEDDS) for a poorly bioavailable drug, valsartan, and to compare their in vivo pharmacokinetics. Proliposomes were prepared by thin-film hydration method using different lipids such as soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoyl phosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. SNEDDS formulations were prepared using varying concentrations of capmul MCM, labrafil M 2125, and Tween 80. Both proliposomes and SNEDDS were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics. In vitro drug release was carried out in purified water and 0.1 N HCl using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal permeation techniques. Among the formulations, the proliposomes with drug/DMPG/cholesterol in the ratio of 1:1:0.5 and SNEDDS with capmul MCM (16.0% w/w), labrafil M 2125 (64.0% w/w), and Tween 80 (18.0% w/w) showed the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes and SNEDDS as compared to pure valsartan. Valsartan permeability across PAMPA and everted rat intestinal permeation models was significantly higher with proliposomes and SNEDDS. Following single oral administration of proliposomes and SNEDDS, a relative bioavailability of 202.36 and 196.87%, respectively, was achieved compared to pure valsartan suspension. The study results indicated that both proliposomes and SNEDDS formulations are comparable in improving the oral bioavailability of valsartan.     

Preparation and Optimization of Fast-Disintegrating Tablet Containing Naratriptan Hydrochloride Using D-Optimal Mixture Design

Optimization of a lyophilized fast-disintegrating tablet (LFDT) formulation containing naratriptan hydrochloride, an antimigraine drug, was the foremost objective of the study, aiming in achieving fast headache pain relief. The Design-Expert® v10 software was used to generate formulations using D-optimal mixture design with four components: gelatin (X₁), hydrolyzed gelatin (X₂), glycine (X₃), and mannitol (X₄) of total solid material (TSM) w/w. The effect of the relative proportion of each component was determined on friability (Y₁), hardness (Y₂), and in vitro disintegration time (Y₃), which was then applied for formulation optimization. In addition, their effect on tablet porosity was determined via scanning electron microscopy (SEM). Drug-excipient interaction was evaluated using differential scanning calorimetry (DSC). A comparative dissolution study against the conventional tablets was studied. Accelerated stability study was carried out in (Al/Al) and (Al/PVC) blister packs. An in vivo pharmacokinetic study was carried out to compare the optimized formulation and the conventional tablets. The optimized formulation’s responses were 0.30%, 3.4 kg, and 6.12 s for Y₁, Y₂, and Y₃, respectively. No drug-excipient interaction was specified via DSC. The optimized formulation exhibited porous structure as determined via SEM. Dissolution study demonstrated complete dissolution within 1.5 min. Study indicated stability for 78 months in (Al/Al) blister packs. In vivo pharmacokinetic study demonstrated that C_max, AUC_last, and AUC_inf were significantly higher for the developed formulation. As well, the T_max was 1 h earlier than that of convenient tablet. An LFDT would achieve a faster onset of action for naratriptan compared to other formulations.     

Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry

An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (>?80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.     

Development of Oral Flexible Tablet (OFT) Formulation for Pediatric and Geriatric Patients: a Novel Age-Appropriate Formulation Platform

Development of palatable formulations for pediatric and geriatric patients involves various challenges. However, an innovative development with beneficial characteristics of marketed formulations in a single formulation platform was attempted. The goal of this research was to develop solid oral flexible tablets (OFTs) as a platform for pediatrics and geriatrics as oral delivery is the most convenient and widely used mode of drug administration. For this purpose, a flexible tablet formulation using cetirizine hydrochloride as model stability labile class 1 and 3 drug as per the Biopharmaceutical Classification System was developed. Betadex, Eudragit E100, and polacrilex resin were evaluated as taste masking agents. Development work focused on excipient selection, formulation processing, characterization methods, stability, and palatability testing. Formulation with a cetirizine-to-polacrilex ratio of 1:2 to 1:3 showed robust physical strength with friability of 0.1% (w/w), rapid in vitro dispersion within 30 s in 2–6 ml of water, and 0.2% of total organic and elemental impurities. Polacrilex resin formulation shows immediate drug release within 30 min in gastric media, better taste masking, and acceptable stability. Hence, it is concluded that ion exchange resins can be appropriately used to develop taste-masked, rapidly dispersible, and stable tablet formulations with tailored drug release suitable for pediatrics and geriatrics. Flexible formulations can be consumed as swallowable, orally disintegrating, chewable, and as dispersible tablets. Flexibility in dose administration would improve compliance in pediatrics and geriatrics. This drug development approach using ion exchange resins can be a platform for formulating solid oral flexible drug products with low to medium doses.     

Early Stage HIV Management and Reduction of Stavudine-Induced Hepatotoxicity in Rats by Experimentally Developed Biodegradable Nanoparticles

The objectives of this research work were to develop optimized nanoparticulate formulations of poly (d,l-lactic-co-glycolic acid) (PLGA) (85:15) with an anti-AIDS drug stavudine and to evaluate their in-vitro uptake by the macrophages and hepatotoxicity in-vivo. Nanoparticles were prepared by nanoprecipitation method based on a factorial design with varying parameters such as the amounts of polymer and stabilizer used. Physicochemical characterizations such as drug–excipient interaction, surface morphology, particle size, and zeta potential measurements were carried out. The best formulation was selected and tagged with fluorescein isothiocyanate (FITC) for cellular uptake study of the formulation. In-vitro uptake of nanoparticles by macrophages was carried out. Formulation-induced hepatotoxicity was assessed by analyzing some serum hepatotoxic parameters and hepatic histology following 10-day treatment in comparison with the free drug. Nanoparticles exhibited smooth surface with particle size 84–238 nm, high entrapment efficiency (approx 85%), and negative surface charge. Formulations showed a sustained drug release pattern over the study period. In-vitro uptake study by macrophages exhibited a time-dependent profile. In-vivo studies on rats showed improvement in the serum parameters and maintenance of the integrity of the hepatic architecture indicating decreased hepatotoxicity with the formulations as compared to the free drug. The experimental results showed a positive outcome in the development of antiretroviral drug carrier exhibiting sustained drug release, macrophage-targeted delivery characteristics, and having reduced hepatoxicity. This could be beneficial for the management of early stage of HIV infection besides reducing the drug load for effective treatment, thereby offering an attractive option in AIDS therapy.     

Improved Skin Penetration Using <Emphasis Type="Italic">In Situ</Emphasis> Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Studies

Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163–165 cps for hydrogel containing microsize drug particles and 171–173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.     

Development of Microemulsions and Microemulgels for Enhancing Transdermal Delivery of <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> Extract

The purpose of this research was to develop microemulsions (ME) and microemulgels (MG) for enhancing transdermal delivery of Kaempferia parviflora (KP) extract. The methoxyflavones were used as markers. Various formulations of ME and MG containing 10% w/v KP extract were prepared, and the in vitro skin permeation and deposition were investigated. The potential ME system containing oleic acid (5% w/v), Tween 20 (20% w/v), PG (40% w/v), and water (35% w/v) was successfully formulated. ME with 10% w/v limonene (ME-L10%) showed higher methoxyflavones flux than ME-L5%, ME-L1%, ME without limonene, and KP extract in water, respectively. ME-L10% was selected for adding a gelling agent to form microemulgels (MG-L10%). However, the high viscosity of the gel formulation might control the diffusion of the compound from gel layer into the skin. Therefore, the liquid formulation provided potential ME droplets to deliver KP extract through the skin. Limonene also plays an effective role on the skin permeation, in which the histological image of the skin treated with ME-L10% exhibited larger space of each flattened keratinocyte layer in the stratum corneum compared to the skin treated with KP extract in water. Moreover, ME-L10% showed good stability. Therefore, ME-L10% was a potential formulation for improving transdermal delivery of KP extract.     

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles

Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a “combo” approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S _z), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A?=?0.04, D/L?=?0.03, and Tw20?=?2.50%?w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0?±?0.9 nm, ζ-potential of ?24.2?±?1.2 mV, and DL and EE of 2.9?±?0.1 and 97.6?±?0.1%?w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.     

Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> evaluation

Lutein is widely used as diet supplement for prevention of age-related macular degeneration. However, the application and efficacy of lutein in food and nutritional products has been hampered due to its poor solubility and low oral bioavailability. This study aimed to develop and evaluate the formulation of oral fast-dissolving film (OFDF) containing lutein nanocrystals for enhanced bioavailability and compliance. Lutein nanocrystals were prepared by anti-solvent precipitation method and then encapsulated into the films by solvent casting method. The formulation of OFDF was optimized by Box-Behnken Design (BBD) as follows: HPMC 2.05% (w/v), PEG 400 1.03% (w/v), Cremophor EL 0.43% (w/v). The obtained films exhibited uniform thickness of 35.64 ± 1.64 μm and drug content of 0.230 ± 0.003 mg/cm² and disintegrated rapidly in 29 ± 8 s. The nanocrystal-loaded films with reconstituted particle size of 377.9 nm showed better folding endurance and faster release rate in vitro than the conventional OFDFs with raw lutein. The microscope images, thermograms, and diffractograms indicated that lutein nanocrystals were highly dispersed into the films. After administrated to SD rats, t _max was decreased from 3 h for oral solution formulation to less than 0.8 h for OFDF formulations, and C _max increased from 150 ng/mL for solution to 350 ng/mL for conventional OFDF or 830 ng/mL for nanocrystal OFDF. The AUC _0-24h of conventional or nanocrystal OFDF was 1.37 or 2.08-fold higher than that of the oral solution, respectively. These results suggested that drug nanocrystal-loaded OFDF can be applied as a promising approach for enhanced bioavailability of poor soluble drugs like lutein.     

Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.     

Novel Strategy to Fabricate Floating Drug Delivery System Based on Sublimation Technique

The present study aims to develop floating drug delivery system by sublimation of ammonium carbonate (AMC). The core tablets contain a model drug, hydrochlorothiazide, and various levels (i.e., 0–50% w/w) of AMC. The tablets were then coated with different amounts of the polyacrylate polymers (i.e., Eudragit® RL100, Eudragit® RS100, and the mixture of Eudragit® RL100 and Eudragit® RS100 at 1:1 ratio). The coated tablets were kept at ambient temperature (25°C) or cured at 70°C for 12 h before further investigation. The floating and drug release behaviors of the tablets were performed in simulated gastric fluid USP without pepsin at 37°C. The results showed that high amount of AMC induced the floating of the tablets. The coated tablets containing 40 and 50% AMC floated longer than 8 h with a time-to-float of about 3 min. The sublimation of AMC from the core tablets decreased the density of system, causing floating of the tablets. The tablets coated with Eudragit® RL100 floated at a faster rate than those of Eudragit® RS100. Even the coating level of polymer did not influence the time-to-float and floating time of coated tablets containing the same amount of AMC, the drug release from the tablets coated with higher coating level of polymer showed slower drug release. The results suggested that the sublimation technique using AMC is promising for the development of floating drug delivery system.     

<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of a PEO-Gellan Gum Semi-Interpenetrating Polymer Network for the Oral Delivery of Sulpiride

In this study, an optimized epichlorohydrin-crosslinked semi-interpenetrating polymer network xerogel matrix system (XePoMas) for the controlled delivery of sulpiride was prepared. The ability of XePoMas to sustain drug release was determined by in vitro and in vivo drug release experiments. Swelling of the xerogel over the 24-h experimental period ranged from 346 to 648%; swelling was observed to increase exponentially over the initial 8 h. In vitro drug release depicted a linear zero order drug release profile with an R ² value of 0.9956. The ability of the fabricated XePoMas to sustain drug release and enhance bioavailability of sulpiride in vivo was investigated by evaluating the plasma drug concentration over 24 h in the large pig model. The optimized XePoMas formulation was shown to increase intestinal absorption of sulpiride to a greater extent than the marketed product in vivo, with a C _max of 830.58 ng/mL after 15 h.     

Preparation and Evaluation of Diclofenac Sodium Tablet Coated with Polyelectrolyte Multilayer Film Using Hypromellose Acetate Succinate and Polymethacrylates for pH-Dependent,Modified Release Drug Delivery

Polyelectrolyte multilayer (PEM) film formed due to the electrostatic interaction between oppositely charged polyelectrolytes is of considerable interest because of their potential applications as both drug carriers and surface-modifying agents. In this study, in vitro studies were carried out on polyelectrolyte complexes formulated with Eudragit E (EE) and hypromellose acetate succinate (HPMCAS). The complexes of EE and HPMCAS were formulated by non-stoichiometric method. The prepared IPCs were investigated using Fourier transform infrared spectroscopy. Diclofenac sodium (DS) tablets were prepared and were coated with polymer solution of HPMCAS and EE to achieve pH-dependent and sustained-release tablets. Tablets were evaluated for their physical characteristics and in vitro drug release. The results of pharmacokinetic studies in rabbits showed that the selected formulation (F6) exhibited a delayed peak plasma concentration and marked sustained-release effect of drug in the in vivo drug release in comparison with marketed tablet. The suitable combination of PEM film based on EE and HPMCAS demonstrated potential candidate for targeted release of DS in the lower part of the gastrointestinal (GI) tract.     

Thermosensitive Poloxamer 407/Poly(Acrylic Acid) Hydrogels with Potential Application as Injectable Drug Delivery System

Thermosensitive hydrogels are of great interest for in situ gelling drug delivery. The thermosensitive vehicle with a gelation temperature in a range of 30–36°C would be convenient to be injected as liquid and transform into gel after injection. To prepare novel hydrogels gelling near body temperature, the gelation temperature of poloxamer 407 (PX) were tailored by mixing PX with poly(acrylic acid) (PAA). The gelation behaviors of PX/PAA systems as well as the interaction mechanism were investigated by tube inversion, viscoelastic, shear viscosity, DSC, SEM, and FTIR studies. The gelation temperature of the plain PX solutions at high concentration of 18, 20, and 22% (w/w) gelled at temperature below 28°C, which is out of the suitable temperature range. Mixing PX with PAA to obtain 18 and 20% (w/w) PX with 1% (w/w) PAA increased the gelation temperature to the desired temperature range of 30–36°C. The intermolecular entanglements and hydrogen bonds between PX and PAA may be responsible for the modulation of the gelation features of PX. The mixtures behaved low viscosity liquid at room temperature with shear thinning behavior enabling their injectability and rapidly gelled at body temperature. The gel strength increased, while the pore size decreased with increasing PX concentration. Metronidazole, an antibiotic used for periodontitis, was incorporated into the matrices, and the drug did not hinder their gelling ability. The gels showed the sustained drug release characteristic. The thermosensitive PX/PAA hydrogel could be a promising injectable in situ gelling system for periodontal drug delivery.     

Development and Evaluation of Cetirizine HCl Taste-Masked Oral Disintegrating Tablets

The purpose of the current study was to mask the taste of cetirizine HCl and to incorporate the granules produced in oral disintegrating tablets (ODT). The bitter, active substance was coated by fluidized bed coating using Eudragit® RL30-D at levels between 15% and 40% w/w. The ODTs were developed by varying the ratio of superdisintegrants such as sodium croscarmellose, crospovidone grades and low substituted hydroxypropyl cellulose (L-HPC). A direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets including porosity, hardness, friability and dissolution profiles were further investigated. The in vitro and in vivo evaluation of the tablet disintegration times showed almost identical rapid disintegration below 10 s at the optimal levels of each superdisintegrant. Finally, the taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and tablet palatability.     

A New Role of Fine Excipient Materials in Carrier-Based Dry Powder Inhalation Mixtures: Effect on Deagglomeration of Drug Particles During Mixing Revealed

The potential of fine excipient materials to improve the performance of carrier-based dry powder inhalation mixtures is well acknowledged. The mechanisms underlying this potential are, however, open to question till date. Elaborate understanding of these mechanisms is a requisite for rational rather than empirical development of ternary dry powder inhalation mixtures. While effects of fine excipient materials on drug adhesion to and detachment from surfaces of carrier particle have been extensively investigated, effects on other processes, such as carrier–drug mixing, capsule/blister/device filling, or aerosolization in inhaler devices, have received little attention. We investigated the influence of fine excipient materials on the outcome of the carrier–drug mixing process. We studied the dispersibility of micronized fluticasone propionate particles after mixing with α-lactose monohydrate blends comprising different fine particle concentrations. Increasing the fine (D < 10.0 μm) excipient fraction from 1.84 to 8.70% v/v increased the respirable drug fraction in the excipient–drug mixture from 56.42 to 67.80% v/v (p < 0.05). The results suggest that low concentrations of fine excipient particles bind to active sites on and fill deep crevices in coarse carrier particles. As the concentration of fine excipient particles increases beyond that saturating active sites, they fill the spaces between and adhere to the surfaces of coarse carrier particles, creating projections and micropores. They thereby promote deagglomeration of drug particles during carrier–drug mixing. The findings pave the way for a comprehensive understanding of contributions of fine excipient materials to the performance of carrier-based dry powder inhalation mixtures.