Aprotinin revisited: formulation, characterization, biodistribution and therapeutic potential of new aprotinin microemulsion in acute pancreatitis.

The aim of this study was to develop aprotinin-loaded microemulsion (MA) for intravenous administration and evaluate the biodistribution and therapeutic potential of developed formulation in acute pancreatitis models in rats. Phase diagrams were constructed to identify microemulsion region and the optimal microemulsion was evaluated for physicochemical properties and treatment effect in rats, and comparisons made with the solution of aprotinin (SA). To evaluate the biodistribution of the drug by gamma scintigraphy aprotinin was radiolabeled with (99m)Tc radionuclide.

Quality by design approach: application of artificial intelligence techniques of tablets manufactured by direct compression.

The publication of the International Conference of Harmonization (ICH) Q8, Q9, and Q10 guidelines paved the way for the standardization of quality after the Food and Drug Administration issued current Good Manufacturing Practices guidelines in 2003. "Quality by Design", mentioned in the ICH Q8 guideline, offers a better scientific understanding of critical process and product qualities using knowledge obtained during the life cycle of a product. In this scope, the "knowledge space" is a summary of all process knowledge obtained during product development, and the "design space" is the area in which a product can be manufactured within acceptable limits.

A quality by design approach using artificial intelligence techniques to control the critical quality attributes of ramipril tablets manufactured by wet granulation.

Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA).

In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation.

Objectives: This study describes the in-situ gelling of econazole nitrate containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel treatment platform for vaginal candidiasis.

Methods: Aqueous thermosensitive formulations containing 1% of econazole nitrate and poloxamer 407 and/or 188 were prepared and their rheological, mechanical and drug-release properties determined at 20 ± 0.1°C and/or 37 ± 0.

In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations.

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer.

Synthesis and characterization of surface-modified PBLG nanoparticles for bone targeting: in vitro and in vivo evaluations.

In this study, poly(γ-benzyl-l-glutamate) (PBLG) polypeptide derivatives were synthesized by ring-opening polymerization of amino acid N-carboxyanhydride using selected amine-terminated initiators. Alendronate, a targeting moiety that has a strong affinity for bone, was conjugated to PBLG. Monomethoxy polyethylene glycol (PEG) was used for a hydrophilic layer on the surface of the nanoparticles (NPs) to avoid reticuloendothelial system uptake.

A comprehensive in vitro and in vivo evaluation of thiolated matrix tablets as a gastroretentive delivery system.

The aim of this study was to investigate the potential of thiolated matrix tablets for gastroretentive delivery systems. Poly(acrylic acid)-cysteine (PAA-Cys) and chitosan-4-thiobuthylamidine (chitosan-TBA) were evaluated as anionic and cationic thiolated polymers and riboflavin was used as a model drug. Tablets were prepared by direct compression and each formulation was characterized in terms of disintegration, swelling, mucoadhesion, and drug release properties.

Pegylation of poly(γ-benzyl-L-glutamate) nanoparticles is efficient for avoiding mononuclear phagocyte system capture in rats.

Poly(γ-benzyl-L-glutamate) (PBLG) derivatives are synthetic polypeptides for preparing nanoparticles with well controlled surface properties. The aim of this paper was to investigate the biodistribution of pegylated PBLG in rats. For this purpose, nanoparticles were prepared by a nanoprecipitation method using mixtures of different PBLG derivates, including a pegylated derivate to avoid mononuclear phagocyte system uptake.

Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base.

This study described the thermosensitive formulations composed of poloxamer mixtures for use as drug delivery platform via mucosal route. It also characterized the poloxamer mixtures' rheological, mechanical and mucoadhesive properties. Poloxamer (Plx) 407 and Plx 188 were used alone and together for preparing the mucosal drug delivery platform.

In vitro and in vivo evaluation of oral tablet formulations prepared with ketoconazole and hydroxypropyl-beta-cyclodextrin.

The objective of this study was to enhance the solubility, dissolution rate, and oral bioavailability of a very poorly water-soluble anti-fungal agent, ketoconazole (KET), by inclusion complexation with a highly-soluble cyclodextrin derivative, hydroxypropyl-beta cyclodextrin (HP-beta-CD). Two groups of tablets containing KET alone and KET:HP-beta-CD (1:2) kneaded product (KP) including magnesium stearate and lactopress (anhydrous and spray-dried) as excipients were prepared by direct compression method. After the characterization studies, the in vitro dissolution studies of these tablets in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were carried out.

Gastroretentive particles formulated with thiomers: development and in vitro evaluation.

The objective of this study is to develop and evaluate gastroretentive particulate delivery systems using Riboflavin-5'-monophosphate sodium salt dihydrate (RF5'PNa) as model drug. Poly(acrylic acid)-cysteine and chitosan-4-thiobuthylamidine were evaluated and compared as anionic and cationic polymers for gastroretentive particles. Permeation studies were performed with freshly excised stomach mucosa from rats.

Cyclosporine a-loaded solid lipid nanoparticles: ocular tolerance and in vivo drug release in rabbit eyes.

Purpose: To determine the in vivo efficacy of cyclosporine A-loaded solid lipid nanoparticles (SLNs) in rabbit eyes.

Methods: SLNs were prepared and administered to the cul-de-sac of rabbits, and the drug amount in aqueous humor was detected by high performance liquid chromatography (HPLC). The irritation was evaluated by modified Draize testing.

Enhanced topical delivery of terbinafine hydrochloride with chitosan hydrogels.

Chitosan-based carriers have important potential applications for the administration of drugs. In the present study, topical gel formulations of terbinafine hydrochloride (T-HCl) were prepared using different types of chitosan at different molecular weight, and the antifungal inhibitory activity was evaluated to suggest an effective formulation for the treatment of fungal infections. The characteristics of gel formulations were determined with viscosity measurements and texture profile analysis.

Studies on mefenamic acid microparticles: formulation, in vitro release, and in situ studies in rats.

In this study, we investigated the in vitro characteristics of mefenamic acid (MA) microparticles as well as their effects on DNA damage. MA-loaded chitosan and alginate beads were prepared by the ionotropic gelation process. Microsponges containing MA and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method.

Cyclosporine A loaded SLNs: evaluation of cellular uptake and corneal cytotoxicity.

Cyclosporine A (CsA) loaded solid lipid nanoparticles (SLNs) for topical ophthalmic applications were prepared by high shear homogenization and ultrasound method using Compritol 888 ATO, Poloxamer 188 and Tween 80, to investigate the cellular uptake of rabbit corneal epithelial cells (RCE) and to evaluate the cytotoxicity. The size of the optimized formulation was 225.9+/-5.

The absorption of (99m)Tc-alendronate given by rectal route in rabbits.

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%-1%).

Permeation studies of indomethacin from different emulsions for nasal delivery and their possible anti-inflammatory effects.

The purpose of this research was to develop an emulsion formulation of indomethacin (IND) suitable for nasal delivery. IND was incorporated into the oil phases of oil in water (O/W) and water in oil (W/O) emulsions. For this purpose, different emulsifying agents (Tween 80, Span 80 and Brij 58) were used in two emulsion formulations.

Comparison of different water/oil microemulsions containing diclofenac sodium: preparation, characterization, release rate, and skin irritation studies.

The aim of the present study was to make a comparison of the in vitro release rate of diclofenac sodium (DS) from microemulsion (M) vehicles containing soybean oil, nonionic surfactants (Brij 58 and Span 80), and different alcohols (ethanol [E], isopropyl alcohol [I], and propanol [P]) as cosurfactant. The optimum surfactant:cosurfactant (S:CoS) weight ratios and microemulsion areas were detected by the aid of phase diagrams. Three microemulsion formulations were selected, and their physicochemical properties were examined for the pH, viscosity, and conductivity.

In vitro release--in vivo microbiological and toxicological studies on ketoconazole lipid granules.

In some multidrug therapy programs, ketoconazole (KTZ) may be administered with some antacids that could modify its dissolution rate and reduce its absorption, thus leading to therapeutic failures. The primary aim of this study was to evaluate the influence of Compritol HD5 ATO and Compritol 888 ATO on this interaction in comparison with commercial KTZ tablets. The second aim was to prepare lipid granules of KTZ that could be an alternative to the commercial formulation.

Controlled release of methotrexate from w/o microemulsion and its in vitro antitumor activity.

The objective of this study was to prepare the microemulsion of methotrexate (M-MTX) for oral use and to investigate the suppressive effect of MTX-loaded microemulsion on MCF-7 human breast cancer cells. At the same time this effect of M-MTX was compared with those of a solution of the drug (Sol-MTX). Microemulsion was composed of soybean oil as oil phase, a mixture of Cremophore EL and Span 80 as surfactants, and isopropyl alcohol as co-surfactant, and 0.

Transdermal delivery of diclofenac sodium through rat skin from various formulations.

The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of w/o microemulsion (M) and gel (G) bases for diclofenac sodium (DS). The effect of dimethyl sulfoxide (DMSO) as a penetration enhancer was also examined when it was added to the M formulation. To study the in vitro potential of these formulations, permeation studies were performed with Franz diffusion cells using excised dorsal rat skin.

Dissolution characteristics of megaloporous tablets prepared with two kinds of matrix granules.

The purpose of this study is to obtain a drug release at a constant rate with a megaloporous tablet, which was prepared with a simple formulation. These tablets were prepared with two kinds of granules. One of them is the restraining-phase matrix granule (RMG) and it controls the release rate of the drug.

Efficacy of a new ketoconazole bioadhesive vaginal tablet on Candida albicans.

To develop more effective treatment for vaginal candidasis, ketoconazole (KTZ) was formulated in bioadhesive tablet formulations that increase the time of contact of drug with the vaginal mucosa. The bioadhesive vaginal tablets delivery of KTZ was prepared by direct compression of sodium carboxymethyl cellulose or polyvinylpyrrolidone or hydroxypropylmethyl cellulose (HPMC-E(50)). Dissolution studies of bioadhesive tablets and commercial ovules were carried out with a new basket method (horizontal rotating basket).

Extended release lipophilic indomethacin microspheres: formulation factors and mathematical equations fitted drug release rates.

Extended release liphophilic microspheres of indomethacin were prepared using cetostearyl alcohol (CsA), stearyl alcohol (SA) and cetyl alcohol (CA) in the various drug-lipid ratios. The release of indometacin was studied on the basis of USP criteria and the effects of drug-lipid ratio, the size of microspheres and carboxymethylcellulose sodium (CMC-Na) added as a hydrophilic polymer on the drug release were investigated. In vitro dissolution studies were performed using USP XXIII apparatus I at pH 6.