Drug Permeation Studies Research Articles

Intranasal delivery of tetrabenazine nanoemulsion via olfactory region for better treatment of hyperkinetic movement associated with Huntington’s disease: Pharmacokinetic and brain delivery study

Tetrabenazine reduces chorea symptoms associated with Huntington’s disease by depleting monoamines in pre-synaptic vesicles. It exhibits low aqueous solubility and undergoes first pass metabolism due to which it has low oral bioavailability. The aim of present work was to formulate intranasal tetrabenazine loaded nanoemulsion for better management and treatment of hyperkinesia related with Huntington’s disease. A quality by design (QbD) technique was employed as statistical multivariate approach for formulation and optimization of nanoemulsion. Optimized formulation showed droplet size of 106.80 ± 1.96 nm with polydispersity index (PDI) value of 0.198 ± 0.005 and -9.63 ± 0.63 mV zeta potential. Ex-vivo drug permeation studies were carried out and found that the formulation has an augmented permeation by 1.68 times as compared to tetrabenazine suspension. MTT assay on neuro-2a cell lines showed that tetrabenazine loaded nanoemulsion displayed better cell viability than placebo and aqueous drug solution at ½ × Cmax, Cmax and 2 × Cmax. Pharmacokinetic parameters in brain after intranasal administration of tetrabenazine nanoemulsion were found to be Cmax = 3.497 ± 0.275 μg/mL, AUC0−12 = 29.196 ± 0.870 μg h/mL and elimination rate constant (ke) = 0.097 ± 0.012 h−1 where as in plasma the pharmacokinetic parameters were Cmax = 1.400 ± 0.084 μg/mL, AUC0−12 = 12.925 ± 0.340 μg h/mL and ke = 0.061 ± 0.010 h−1. Histopathological studies of porcine nasal mucosa showed that nasal mucosa remains intact when treated with tetrabenazine loaded nanoemulsion. Thus it can be concluded from study that optimized nanoemulsion formulation of a tetrabenazine was robust and its delivery through nasal route is a viable alternative to other routes of administration for treatment of hyperkinesia associated with Huntington’s disease.

Microflow-Based Device for In Vitro and Ex Vivo Drug Permeability Studies.

This paper presents a novel microflow-based concept for studying the permeability of in vitro cell models or ex vivo tissues. Using the proposed concept, we demonstrate how to maintain physiologically relevant test conditions and produce highly reproducible permeability values for a range (31) of drug compounds. The apparent permeability coefficients (Papp) showed excellent correlation (0.89) with the values from experiments performed with a conventional Ussing chamber. Additionally, the microflow-based concept produces notably more concentrated samples than the conventional Ussing chamber-based approach, despite the fact that more than 10 times smaller quantities of test compounds and biological membranes are needed in the microflow-based concept.

Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug.

The transdermal delivery of sparingly soluble drugs is challenging due to of the need for a drug carrier. In the past few decades, ionic liquid (IL)-in-oil microemulsions (IL/O MEs) have been developed as potential carriers. By focusing on biocompatibility, we report on an IL/O ME that is designed to enhance the solubility and transdermal delivery of the sparingly soluble drug, acyclovir. The prepared MEs were composed of a hydrophilic IL (choline formate, choline lactate, or choline propionate) as the non-aqueous polar phase and a surface-active IL (choline oleate) as the surfactant in combination with sorbitan laurate in a continuous oil phase. The selected ILs were all biologically active ions. Optimized pseudo ternary phase diagrams indicated the MEs formed thermodynamically stable, spherically shaped, and nano-sized (<100 nm) droplets. An in vitro drug permeation study, using pig skin, showed the significantly enhanced permeation of acyclovir using the ME. A Fourier transform infrared spectroscopy study showed a reduction of the skin barrier function with the ME. Finally, a skin irritation study showed a high cell survival rate (>90%) with the ME compared with Dulbecco’s phosphate-buffered saline, indicates the biocompatibility of the ME. Therefore, we conclude that IL/O ME may be a promising nano-carrier for the transdermal delivery of sparingly soluble drugs.

Exploration of neem gum-chitosan and kheri gum-chitosan polyelectrolyte complex based film for transdermal delivery of protein/peptide

Present investigation is continuation of author’s previously published work. In the present investigation, the author has prepared neem gum-chitosan and kheri gum-chitosan polyelectrolyte complex transdermal film for the delivery of protein/peptide drug. Concentration of gum (neem gum and kheri gum) and chitosan was varied in each concentration while drug concentration kept constant. Albumin was used as a model protein drug. Transdermal films were fabricated using a solvent casting method without using any plasticizer and evaluated for various parameters viz. folding endurance, surface pH, weight variation, drug content, percentage moisture content, surface morphology, in vitro drug release and ex vivo drug permeation study. The study showed that films were successfully fabricated with good acceptable physical properties. In vitro drug release study and ex vivo drug permeation study showed that polyelectrolyte films were able to extend drug delivery up to 9 days. It can be easily concluded from the findings of the results that neem gum-chitosan and kheri gum-chitosan polyelectrolyte complex films can be easily prepared without using any plasticizer and able to deliver protein/peptide therapeutic agents for an extended period of time.

Enantioselectivity on the absorption of methylone and pentedrone using Caco-2 cell line: Development and validation of an UHPLC method for cathinones quantification

Synthetic cathinones, such as methylone and pentedrone, are psychoactive derivatives of cathinone, sold in the internet as “plant food” or “bath salts”.However, the level at which these compounds and their enantiomers cross the intestinal barrier has not been yet determined. Thus, the present study aimed to analyze the enantioselectivity on the permeability of these drugs through the intestinal barrier by using the Caco-2 cell line, a widely used in vitro model for drug permeability studies. To achieve this goal, an UHPLC-UV method was developed and validated to quantify both synthetic cathinones.The developed UHPLC-UV method revealed high selectivity and a linearity from 1 to 500 μM with correlation coefficients always higher than 0.999. The method has an accuracy that ranged between 89 and 107%, inter-day and intra-day precisions with coefficients of variation below 10%, limits of detection and quantification of 0.31 μM and 0.93 μM for methylone and 0.17 μM and 0.52 μM for pentedrone, respectively. In Caco-2 cells, a differentiated passage of the enantiomers across monolayer was observed for both cathinones. For pentedrone, the difference was observed after the first hour, being R-(−)-pentedrone the most permeable compound. Regarding methylone, the difference was noted after one hour and 30 min, with S-(−)-methylone being the most absorbed enantiomer.In conclusion, a fully validated method was successfully applied for studying the permeability of methylone and pentedrone enantiomers in an in vitro model of human intestine, which allowed to discover, for the first time, the enantioselectivity in drug permeability of this class of drugs.

Formulation, Optimization and Characterization of Chitosan Monodisperse Microparticles for Sustained Delivery of Hydrochlorothiazide HCl

Background: Hydrochlorothiazide HCl (HCTZ) is first line medication in the management of hypertension, however its poor solubility and GI irritation warrants long term application. The aim of present study was to prepare hydrochlorothiazide HCl (HCTZ) loaded monodisperse microparticles of chitosan (CS) for sustained delivery. Methods: In the present study chitosan microparticle were prepared using ionic gelation method. The effect of input parameters such as concentration of chitosan and pH of CS solution on the mean particle size (PS), zeta potential (ZP), polydispersity index (PDI) and in-vitro drug release were investigated. In-vitro drug release from the microparticles was studied using Franz diffusion cell. Structural formation and surface morphology was investigated using FTIR and SEM, respectively. Results: PS of CS microparticles ranges from 0.878±0.066 to 1.963±0.011 µm, ZP between 33.43±0.80 mV to 53.6±2.06 mV, PDI values from 0.271±0.063 to 0.842±0.073. The optimized CSMP- 3 (1.5% chitosan, pH 3) showed PS 1.672 ± 0.073 µm, ZP 53.6 ±2.06 mV, PdI 0.481±0.053, %EE 80.8±2.27% and HCTZ release of around 80% in 8 hours. FTIR reveals successful formation of crosslinked structure. SEM shows irregular surface owing preparation procedure. Drug kinetics modeled with Korsemeyer–Peppas equation revealed non-Fickian diffusion mechanism. Conclusion: Drug permeation study showed more than 70% of drug permeated through membrane. In conclusion, the CS microparticles can be used for the sustained delivery of HCTZ which would reduce the dosing frequency and improved patient compliance.

Non-invasive drug delivery system for the delivery of protein/peptide using neem gum and its derivatives

The present investigation is continuation of author’s previous work. In previous work, the author was prepared acrylamide grafted copolymer of neem gum and carboxymethylatedneem gum derivatives. Neem gum polysaccharide (NGP) and its derivatives viz. acrylamide grafted neem gum (NGP-g-Am) and carboxymethylated neem gum (CMNGP) were explored as film forming agent for transdermal delivery of protein/peptide drug (albumin). It was observed that films were not prepared at all the concentrations of NGP with a given concentration range. Studies show that film cannot be prepared using CMNGP even at ahigher concentration of polymer (2 % w/v solution). So only acrylamide grafted neem gum based film were prepared and evaluated. Transdermal films were prepared by using solvent casting method. The developed films were evaluated for various parameters such as drug content, folding endurance, thickness, weight variation, surface pH, moisture uptake, in vitro drug release study and ex-vivo permeation study. The films showed more than 300 folding endurance which demonstrated the good mechanical strength of film. It was also observed that after permeation studies small cracks were also formed in the films. Fabricated films were able to deliver drug upto 7 h. Drug release study and drug permeation studies showed that formulations followed zero order and KorsmeyerPepass model of kinetics. It can be concluded from the findings of the results that acrylamide graft copolymers of neem gum were able to deliver protein/peptide drugs through transdermal route.

Development and Characterization of Water-in-Oil Microemulsion for Transdermal Delivery of Eperisone Hydrochloride

Background: Eperisone hydrochloride possesses short biological half-life due to first pass metabolism resulting in low bioavailability and short duration of response with toxic effects, ultimately limits its utilization for treatment of muscle spasm. Objective: In view of this background, current study was designed for the development of Eperisone hydrochloride-loaded microemulsion and Eperisone hydrochloride-loaded microemulsion based cream for topical delivery and compared it with conventional cream. Methods: Firstly, water-in-oil microemulsion was prepared by spontaneous emulsification method. The concentration of components was found out from existence of microemulsion region by constructing pseudoternary phase diagram. The oil was selected on the basis of drug solubility effect on the drug release, whereas surfactant and cosurfactant were screened on the basis of their efficiency to form microemulsion region. The influence of components on microemulsion formation, drug release capacity, permeation was studied by differential scanning calorimetry, X-ray diffraction, in-vitro release and ex-vivo drug permeation studies respectively. By using microemulsion, the cream was prepared for proving optimum structure for topical application. Microemulsion was evaluated for droplet size, zeta potential, pH, viscosity and conductivity. Besides the cream was characterized for pH, rheology and stability. Permeation of EPE from microemulsion across the rat skin was evaluated and compared with conventional cream. Results: The microemulsion consisting Isopropyl Myristrate/Water/Span 80:Tween 80 (50/8/42% by weight) possessed droplet size of 95.77nm, zeta potential of −5.23 mV with 7.25 pH and conductivity near to zero (&lt;0.05mScm-1). Physical parameters of the cream were satisfactory, also 2.33-fold higher permeation and 1.57-fold higher release observed as compared to conventional cream. Conclusion: It can be concluded that Eperisone hydrochloride-loaded microemulsion and its cream is being effectively used for muscle spasticity by topical route.

A dynamic perfusion based blood-brain barrier model for cytotoxicity testing and drug permeation

The blood-brain barrier (BBB) serves to protect and regulate the CNS microenvironment. The development of an in-vitro mimic of the BBB requires recapitulating the correct phenotype of the in-vivo BBB, particularly for drug permeation studies. However the majority of widely used BBB models demonstrate low transendothelial electrical resistance (TEER) and poor BBB phenotype. The application of shear stress is known to enhance tight junction formation and hence improve the barrier function. We utilised a high TEER primary porcine brain microvascular endothelial cell (PBMEC) culture to assess the impact of shear stress on barrier formation using the Kirkstall QuasiVivo 600 (QV600) multi-chamber perfusion system. The application of shear stress resulted in a reorientation and enhancement of tight junction formation on both coverslip and permeable inserts, in addition to enhancing and maintaining TEER for longer, when compared to static conditions. Furthermore, the functional consequences of this was demonstrated with the reduction in flux of mitoxantrone across PBMEC monolayers. The QV600 perfusion system may service as a viable tool to enhance and maintain the high TEER PBMEC system for use in in-vitro BBB models.

Herbal ethosomal gel containing luliconazole for productive relevance in the field of biomedicine.

This study includes development, characterization, and optimization of herbal ethosomal formulation. The aim of the present study is to develop drug loaded ethosomes capped with Azadirachta indica (neem) which, was further incorporated in Carbopol 934K thereby, resulting in the formation of ethosomal gel. The formulation is aimed to express effective treatment against fungal infection. The build was formulated using drug (Luliconazole), soyalecithin, ethanolic neem extract and propylene glycol. In total nine ethosomal, formulations of distinct concentrations of ingredients were processed, to determine out the optimized formulation among the all. Further the prepared drug loaded ethosomes were subjected to various evaluation parameters like particle size, zeta potential, polydispersity index (PDI) and % entrapment efficiency. For the evaluation of its surface morphology, transmission electron microscopy was executed whereas, atomic force microscopy was carried out which contributes in detail and depth information of surface morphology. For the analysis of thermal behavior Thermal gravimetric analysis graph was obtained for luliconazole, soyalecithin, neem extract, physical mixture and optimized formulation (LF5). Attenuated total internal reflection Fourier transforms infra-red spectroscopy was performed for luliconazole, soyalecithin, neem extract, physical mixture, and optimized formulation (LF5) to examine the interaction between the drug and the excipients. Viscosity, pH, spreadability and extrudability of the ethosomal gel were calculated to determine the suitability of the formulation for topical application. In vitro drug permeation study and antifungal activity was executed out with the aid of Wistar albino rat skin model and tube dilution assay respectively. The complete study wrap up, that this herbal ethosomal approach provides advanced sustained and targeted delivery of luliconazole. On analyzing the results, ethosomal formulation LF5 was found to be optimized one, due to its optimum concentration of soyalecithin (300mg) and ethanol (35%). Hence it has maximum entrapment efficiency of 86.56 ± 0.74%. Optimum vesicle size, zeta potential, and PDI were found to be 155.30 ± 1.2nm, -42.20 ± 0.3mV, and 0.186 ± 0.07 respectively. In vitro drug permeation study expresses release of 83.45 ± 2.51 in 24h whereas; the in vivo activity proved that LF5 is more active and effective against Candida parapsilosis in comparison to Aspergillus niger. In the end, it was estimated that ethosomal suspension and lyophilized ethosomal suspension was utmost stable at 4°C/60 ± 5 RH. The complete study clearly indicates that the buildup of ethosomal formulation with luliconazole and neem extract show synergistic effect thereby, expressing excellent result against the treatment of fungal infection.

Formulation and Evaluation of Erythromycin Estolate Loaded Drug Balls

The purpose of research work was to develop and optimize drug balls of erythromycin estolate for oral mucosal delivery of drug for fast delivery of drug and better bio-availability with the aim to treatment of whooping cough with also additional advantages over the traditional dosage forms such as suspension and tablets which takes too much time for release of drug but drug balls release mucoadhesive liquid which shows fast drug release, better bioavailability, avoid hepatic first pass effect and fast action. Sodium alginate based drug balls containing erythromycin estolate were prepared by specific method. Sodium alginate, ethyl cellulose were selected on the basis of formulation of drug balls, mucoadhesive force, In-vitro drug release. A 32 factorial design was employed for preparation of drug balls wherein the concentration of sodium alginate, concentration of ethyl cellulose were selected as independent variables while in vitro drug release and percentage permeation were the dependent variables. Drug balls were evaluated with respect to the percentage mucoadhesion, drug content, invitro drug release and permeation studies. F4 formulation was optimized with mucoadhesive force, %permeation efficiency and In-vitro drug release. Drug balls were characterized by FTIR and DSC study. Stability study revealed that the formulation was found to be stable.

Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits

The present study was focused on investigating niosomal gels loaded with cholinergic drug; pilocarpine HCl, for prolonged precorneal residence time and improved bioavailability for glaucoma treatment. Pilocarpine HCl niosomes were prepared using various nonionic surfactants (span 20, span 60 and span 80), in the presence of cholesterol in different molar ratios by ether injection method. The selected formulations were incorporated into carbopol 934 and locust bean gum-based gels. TEM analysis confirmed that niosomes formed were spherical in shape and has a definite internal aqueous space with uniform particle size. Formulation F4 composed of span 60 and cholesterol (1:1) gave the highest entrapment (93.26 ± 1.75%) and slower release results after 8 hours (Q8h = 60.35 ± 1.87%) among other formulations. The in-vitro drug permeation studies showed that there was a prolonged release of drug from niosomal gels as compared to niosomes itself. Considering the in-vitro drug release, niosomal gel formulation G2 was the best among the studied formulations. The release data were fitted to an empirical equation, which indicated that the release follows non-Fickian diffusion mechanism. The stability study revealed that incorporation of niosomes in gel increased their stability than the niosome itself. No signs of redness, inflammation, swelling or increased tear production were observed over the study period for tested formulation by Draize’s test. The intraocular pressure (IOP) lowering activity of G2 formulation showed relative bioavailability 2.64 times more than bioavailability of marketed Pilopine HS® gel. These results suggest that the niosomal gels containing pilocarpine HCl are promising ocular carriers for glaucoma treatment.

Rational design and in-vivo estimation of Ivabradine Hydrochloride loaded nanoparticles for management of stable angina

Stable angina or angina pectoris is referred to as uneasiness/pain in the chest, resulting from coronary heart disease (CHD). Ivabradine Hydrochloride (IBH) is a recently approved drug to manage stable angina and heart failure symptoms. The approved IBH tablets exhibit some technical shortcomings i.e. short half-life (2 h), variable systemic absorption, and high first-pass metabolism (>50%). Therefore, utilizing a nanoformulation technique, we have designed a differentiated and innovative formulation of IBH. The IBH loaded polymeric nanoparticles (IBH-PNPs) are being developed for per-oral delivery by double emulsion method, using Poly lactic-co-glycolic acid (PLGA) as polymer, and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizer. The pre-formulation studies performed are UV spectroscopy, FT-IR, and X-ray diffraction. The Box-Behnken design was exploited for formulation optimization. The optimized formulation was characterized for its particle size, zeta potential, morphology, entrapment efficiency, in-vitro release, stability studies, ex-vivo permeability, and in-vivo pharmacodynamics study. The optimized IBH-PNPs were found to be spherical (<200nm) and exhibited normal size distribution under transmission electron microscopy and atomic force microscopy respectively. The zeta potential and entrapment efficiency were found to be −43.75 mv and 60 ± 4.8% respectively. Developed IBH-PNPs analyzed for in-vitro drug release where they exhibited biphasic release. The ex-vivo drug permeation study showed 1.85 folds increment in intestinal permeability as compared to IBH tablets. The in-vivo anti-anginal efficacy studies were performed using vasopressin-induced angina model in Wistar rats. Developed formulation was found to have a therapeutic effect for three days.

Formulation and optimization of microemulsion based sparfloxacin in-situ gel for ocular delivery: In vitro and ex vivo characterization

Conventional eye drops have a major limitation of having short residence time in Cul de sac, which is responsible for low bioavailability of the drug and poor therapeutic response. In-situ gel system having a sol-gel transformation is an attractive approach to increase the drug residence time without compromising the advantage of eye drop of easy application. The present investigation was aimed to prepare microemulsified based in-situ gel system of sparfloxacin to improve its solubility and permeability through the cornea. Labrafil M1944 CS, Acrysol–140 and Transcutol-P were used as lipid, surfactant, and co-surfactant respectively to prepare sparfloxacin containing microemulsion. The design batches prepared according to simplex lattice designs were evaluated for globule size, polydispesity index, pH and drug content. Poloxamer 407, a thermo responsive polymer was used as polymer for preparing in situ gel of optimized formulation which was evaluated for clarity, pH, gelling capacity, and the rheological properties. In addition to that ex-vivo drug permeation and ocular irritation studies were also performed. The prepared optimized formulation was found to be clear, stable and non-irritant after 90 days of storage under accelerated stability condition.

Proof-of-Concept Study of Drug Brain Permeability Between in Vivo Human Brain and an in Vitro iPSCs-Human Blood-Brain Barrier Model

The development of effective central nervous system (CNS) drugs has been hampered by the lack of robust strategies to mimic the blood-brain barrier (BBB) and cerebrovascular impairments in vitro. Recent technological advancements in BBB modeling using induced pluripotent stem cells (iPSCs) allowed to overcome some of these obstacles, nonetheless the pertinence for their use in drug permeation study remains to be established. This mandatory information requires a cross comparison of in vitro and in vivo pharmacokinetic data in the same species to avoid failure in late clinical drug development. Here, we measured the BBB permeabilities of 8 clinical positron emission tomography (PET) radioligands with known pharmacokinetic parameters in human brain in vivo with a newly developed in vitro iPSC-based human BBB (iPSC-hBBB) model. Our findings showed a good correlation between in vitro and in vivo drug brain permeability (R2 = 0.83; P = 0.008) which contrasted with the limited correlation between in vitro apparent permeability for a set of 18 CNS/non-CNS compounds using the in vitro iPSCs-hBBB model and drug physicochemical properties. Our data suggest that the iPSC-hBBB model can be integrated in a flow scheme of CNS drug screening and potentially used to study species differences in BBB permeation.

In-vitro blood-brain barrier models for drug screening and permeation studies: an overview.

The blood-brain barrier (BBB) is comprised of brain microvascular endothelial central nervous system (CNS) cells, which communicate with other CNS cells (astrocytes, pericytes) and behave according to the state of the CNS, by responding against pathological environments and modulating disease progression. The BBB plays a crucial role in maintaining homeostasis in the CNS by maintaining restricted transport of toxic or harmful molecules, transport of nutrients, and removal of metabolites from the brain. Neurological disorders, such as NeuroHIV, cerebral stroke, brain tumors, and other neurodegenerative diseases increase the permeability of the BBB. While on the other hand, semipermeable nature of BBB restricts the movement of bigger molecules i.e. drugs or proteins (>500 kDa) across it, leading to minimal bioavailability of drugs in the CNS. This poses the most significant shortcoming in the development of therapeutics for CNS neurodegenerative disorders. Although the complexity of the BBB (dynamic and adaptable barrier) affects approaches of CNS drug delivery and promotes disease progression, understanding the composition and functions of BBB provides a platform for novel innovative approaches towards drug delivery to CNS. The methodical and scientific interests in the physiology and pathology of the BBB led to the development and the advancement of numerous in vitro models of the BBB. This review discusses the fundamentals of BBB structure, permeation mechanisms, an overview of all the different in-vitro BBB models with their advantages and disadvantages, and rationale of selecting penetration prediction methods towards the critical role in the development of the CNS therapeutics.

Formulation and evaluation of thymoquinone niosomes: application of developed and validated RP-HPLC method in delivery system

A rapid, accurate, and sensitive reverse phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the estimation of Thymoquinone (TMQ) in API as well as in noisome. The chromatograms were developed with the mobile phase – water: 2-propanol: methanol (50:45:5 v/v/v) as a solvent system at 254 nm. The method was validated as per ICH guidelines for different parameters and the recovery of TMQ was calculated in developed niosomes. Further, TMQ loaded niosomes (TMQNIOS) were prepared and evaluated for different parameters. The optimized TMQNIOS (F3) was further evaluated for surface morphology, in vitro drug release, permeation study, and confocal laser scanning microscopic (CLSM) study. The method showed linearity range between 6.25 and 100 µg/ml with low detection limit and quantitation limit with a value of 2.08 and 6.25 µg/ml. The developed formulations showed the vesicle size and encapsulation efficiency in the range of 157.32 ± 3.15 to 211.44 ± 5.23 nm and 59.32 ± 4.87 to 83.21 ± 3.55%, respectively. The drug release result showed the significant higher release from TMQNIOS in compared to TMQDIS, and the release kinetics data showed Higuchi's equation with highest regression coefficient values. The permeation study and the confocal laser microscopy study further confirmed the enhancement in permeation of TMQ in the intestinal mucosa.

Sodium caseinate films modified using halloysite: Physicochemical characterization and drug permeability studies

Modification of sodium caseinate (SC) films by adding halloysite (HS) was investigated in this study. SC films with HS added in different ratios were prepared, and the physicochemical properties and drug permeability of the films were characterized. Acetaminophen was used as a model drug, and parabens served to evaluate the effect of the molecular weight of permeants through the films. This study revealed that SC could interact with HS through hydrogen bonding between the amine and amide groups of SC and the hydroxyl groups on the inner or outer tubular HS. The SC-HS films presented as continuous sheets and had a similar transparency as the SC films. The thermal stability of the SC films could be enhanced by adding HS. Incorporation of HS caused a reduction in puncture strength and elongation of the dry SC films, whereas strength enhancement of the wet SC-HS films in acidic medium was found. The SC-HS films had lower water uptake and delayed drug permeation across the films in acidic medium. Moreover, the drug permeations across the SC and SC-HS films were dependent on the molecular weight or alkyl chain of parabens that impacted drug diffusion and partition processes through the films. The new knowledge obtained can be helpful for the development of film coating material based on SC-HS composites for modified-release tablets.

Design and Evaluation of a Poly(Lactide-co-Glycolide)-Based In Situ Film-Forming System for Topical Delivery of Trolamine Salicylate.

Trolamine salicylate (TS) is a topical anti-inflammatory analgesic used to treat small joint pain. The topical route is preferred over the oral one owing to gastrointestinal side effects. In this study, a poly(lactide-co-glycolide) (PLGA)-based in situ bio-adhesive film-forming system for the transdermal delivery of TS was designed and evaluated. Therefore, varying amounts (0%, 5%, 10%, 20%, and 25% (w/w)) of PLGA (EXPANSORB® DLG 50-2A, 50-5A, 50-8A, and 75-5A), ethyl 2-cyanoacrylate, poly (ethylene glycol) 400, and 1% of TS were dissolved together in acetone to form the bio-adhesive polymeric solution. In vitro drug permeation studies were performed on a vertical Franz diffusion cell and dermatomed porcine ear skin to evaluate the distinct formulations. The bio-adhesive polymeric solutions were prepared successfully and formed a thin film upon application in situ. A significantly higher amount of TS was delivered from a formulation containing 20% PLGA (45 ± 4 µg/cm2) and compared to PLGA-free counterpart (0.6 ± 0.2 µg/cm2). Furthermore, the addition of PLGA to the polymer film facilitated an early onset of TS delivery across dermatomed porcine skin. The optimized formulation also enhanced the delivery of TS into and across the skin.

In Vitro and Ex Vivo Evaluation of Tablets Containing Piroxicam-Cyclodextrin Complexes for Buccal Delivery

In the current study, the development of mucoadhesive tablets for buccal delivery of a non-steroidal anti-inflammatory drug was investigated. Binary complexes with piroxicam and cyclodextrins (β-cyclodextrin (β-CD), methylated-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD)) were prepared by the co-evaporation method. All formulations were characterized by means of differential scanning calorimetry, infrared spectroscopy and powder X-ray diffractometry. Mucoadhesive tablets of binary systems were formulated by direct compression using chitosan as mucoadhesive polymer. The in vitro release profiles of tablets were conducted in simulated saliva and, the drug permeation studies, across porcine buccal mucosa. The results suggest that the rank order effect of cyclodextrins for the drug release was Me-β-CD > HP-β-CD > β-CD, whereas the ex vivo studies showed that the tablets containing chitosan significantly increased the transport of the drug compared to their free complexes. Finally, histological assessment revealed loss of the superficial cell layers, which might be attributed to the presence of cyclodextrins.