Diffusion-controlled Drug Delivery Research Articles

Design of diffusion-controlled drug delivery devices for controlled release of Paclitaxel.

Controlled drug delivery devices were predicted in a reverse engineering framework for the controlled release of Paclitaxel, an anti-cancer drug, widely used in the treatment of solid tumors. Using quantitative structure-property relationship models for mutual diffusion coefficients of the drug in biocompatible and biodegradable polymers and partition coefficients of the drug between polymers and blood, a framework was developed to predict optimal drug delivery devices for desired dosage regimens. The validation of the predicted mutual diffusion and partition coefficients using experimental data was reported in previous studies. Optimal design parameters along with selection of most appropriate polymers suitable for different dosage regimens, selected based on current clinical practice, were predicted for maximum bioavailability of the drug while maintaining the released drug concentration in blood within the therapeutic range. Reservoir and monolithic type of diffusion-controlled drug delivery devices of different shapes and sizes were predicted with different initial drug loadings and bioavailability for different dosage regimens. The effects of the released Paclitaxel from these devices on the tumor growth were also modeled using a previously reported mathematical pharmacokinetic-pharmacodynamic model. The proposed approach can easily be used to design other diffusion-controlled drug delivery devices.

Prediction of the partition coefficients using QSPR modeling and simulation of paclitaxel release from the diffusion-controlled drug delivery devices.

An in silico approach is proposed to first predict the partition coefficient of the model drug, paclitaxel, in different biocompatible and biodegradable polymer versus the blood plasma using artificial neural networks (ANNs) and semi-empirical quantitative structure property relationships (QSPRs). A simplified molecular-input line-entry system (SMILES) notation is used to represent the structures of the different polymers and the drug. The SMILES notation is then used to calculate the various structure-based descriptors. These descriptors are then used in the ANNs and semi-empirical QSPRs to predict the properties for a given drug-polymer device. A fluid flow model is subsequently solved to simulate the controlled drug release in the blood plasma. The effects of various parameters are also studied on the drug release profiles from these devices. The proposed approach provides a systematic framework to simulate the controlled release of the drug from the diffusion-controlled drug-polymer release systems. The developed models can be used in a reverse engineer framework to design the controlled delivery devices for a target drug release profile in near future.

СУЧАСНИЙ СТАН СТВОРЕННЯ, ВИРОБНИЦТВА ТА ДОСЛІДЖЕННЯ ТАБЛЕТОВАНИХ ЛІКАРСЬКИХ ПРЕПАРАТІВ. Повідомлення 24. Осмотичні системи вивільнення та доставки лікарських речовин: розробка, характеристика та їх класифікація

Проведено огляд літературних джерел щодо розробки та дослідження осмотичних систем вивільнення та доставки лікарських речовин

Oral controlled release drug delivery system and Characterization of oral tablets; A review

Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets.

S-adenosyl-l-methionine (SAMe)-loaded nanochitosan particles: synthesis, characterisation and in vitro drug release studies

Chitosan-based drug carriers are being widely exploited for sustained and targeted delivery in cancer, anti-depression and nutritive therapeutics. In this paper, we report the preparation of S-adenosyl-l-methionine (SAMe) drug-loaded nanochitosan-based tablets and the sustained delivery of the drug substance in simulated intestinal conditions through an in vitro study. The convertibility of high molecular weight commercial chitosan to nanoparticles by ionic gelation using potassium pyrophosphate was achieved without employing harsh reaction conditions through an intermediate water-soluble chitosan preparation. The prepared nanochitosan particles with an average size of 85–127 nm showed good drug-loading capacity. In vitro release studies showed a continuous and slow release of the drug over 14 hours. Different kinetics models were applied to drug release data in order to evaluate the releasing mechanism. The drug release data fit well into the Higuchi expression, suggesting a diffusion-controlled drug delivery. The diffusional coefficient of 1.83 indicated that the drug release from the chitosan matrix was through swelling of the matrix. Agreement of the kinetic data with Higuchi and Korsmeyer–Peppas models have led us to conclude that the delivery of the SAMe drug from the nanochitosan drug carrier took place by the diffusion-controlled swelling mechanism described as Super case II transport. The prepared nanochitosan matrix was also found to be an environment-sensitive vehicle suitable for controlled drug delivery.

Formulation of sildenafil citrate loaded nasal microsphers: An in vitro, ex vivo characterization.

The aim of the present study was to prepare gellan gum microspheres of Sildenafil citrate, for intranasal delivery to avoid the first pass metabolism. The microspheres were prepared using spray drying method. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swelling ability, zeta potential, in-vitro mucoadhesion, ex-vivo mucoadhesion, thermal analysis, XRD study and in-vitro drug release. Treatment of in-vitro data to different kinetic equations indicated diffusion controlled drug delivery from gellan gum microspheres. The results of DSC and XRD studies revealed the molecular amorphous dispersion of Sildenafil citrate into the gellan gum microspheres. Microspheres so prepared were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 95-98%. The formulation exhibited a good mucoadhesive strength which was determined in in vitro conditions through falling film technique and was compared with ex vivo studies. The microspheres so prepared also exhibited a good swelling index which confirmed the strong mucoadhesive property of the formulation. Keywords: Gellan gum, Microsperes, Spray drying, Sildinafil citrate, Nasal delivery.

Nasal administration of ondansetron using a novel microspheres delivery system

Gellan gum microspheres of ondansetron hydrochloride, for intranasal delivery, were prepared to avoid the first pass metabolism as an alternative therapy to parentral, and to improve therapeutic efficiency in treatment of nausea and vomiting. The microspheres were prepared using conventional spray-drying method. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swelling ability, zeta potential, in-vitro mucoadhesion, thermal analysis, XRD study and in-vitro drug release. Treatment of in-vitro data to different kinetic equations indicated diffusion controlled drug delivery from gellan gum microspheres. The results of DSC and XRD studies revealed molecular amorphous dispersion of ondansetron into the gellan gum microspheres.

Influence of processing and sterilisation on properties of poly-ϵ-caprolactone

Poly-ϵ-caprolactone (PCL) is a significant member of a group of polymers regarded as bioabsorbable, having been the focus of extensive research for use as a diffusion controlled drug delivery system. Degradation of PCL proceeds through hydrolysis of the ester bonds in the polymer chains and is influenced significantly by the polymer's initial molecular weight and crystallinity. To evaluate the effects of processing and sterilisation on these properties, PCL pellets (CAPA 6400) were either injection moulded or extruded and sterilised by ethylene oxide gas (EtO). Procedures were used to evaluate mechanical properties, molecular weight and crystallinity. Upon processing and sterilisation the molecular weights of the injection moulded and extruded materials did not differ significantly from that of the PCL pellets, suggesting processing and sterilisation did not initiate chain scission of the polymer's ester bonds. However, the crystallinity of PCL proved to be sensitive to injection moulding with an increase of approximately 5% observed after processing, with sterilisation by EtO gas causing annealing of the PCL pellets, injection moulded and extruded material. After sterilisation the crystallinity of the PCL pellets and extruded material increased by approximately 10% with a 4% increase observed for the injection moulded material. The mechanical properties of both the injection moulded and extruded material where not influenced by sterilisation. The results from this investigation suggest that PCL's molecular weight is insensitive to processing and sterilisation. However, sterilisation by EtO gas in the temperature range of 38-48°C used in this study does result in annealing of the polymer.

Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine

This work investigates pilocarpine trapped in a matrix diffusion-controlled drug delivery system using hydrophilic inserts of Poly(2-hydroxyethyl methacrylate) (pHEMA) to ensure an increased bioavailability of pilocarpine and prolong the length of time in which the medication remains in the eyes of the test subjects. The physical and chemical properties of pilocarpine were investigated to elucidate the mechanism of drug–polymer interaction and the effect on drug release behavior of controlled release polymeric devices. In vitro release studies indicated that pilocarpine continued to be released from the inserts for a 24 h period. The results of intraocular pressure tests performed on albino rabbits were consistent with the observed in vitro behavior. The pressure decrease was significant for a period longer than 48 h. It confirms that the inserts, as sustainable releasing devices, are promising carriers for ophthalmic drug delivery systems.

Diffusion-controlled drug delivery systems: calculation of the required composition to achieve desired release profiles

The aim of this study was to investigate the effect of the composition of diffusion-controlled release devices (type and amount of plasticizer, type of polymer) on the drug diffusivity and the resulting release kinetics in a quantitative way. Diltiazem hydrochloride and theophylline were investigated in ethyl cellulose (EC) and Eudragit® RS 100, plasticized with various amounts of acetyltributyl citrate (ATBC), acetyltriethyl citrate (ATEC), dibutyl phthalate (DBP), dibutyl sebacate (DBS), diethyl phthalate (DEP), and tributyl citrate (TBC). Thin drug-containing films (monolithic solutions) were used to determine the diffusion coefficients experimentally. The effect of the type and amount of plasticizer on the drug diffusivity was found to be significant, whereas the chain length of the polymer only played a minor rule in the investigated systems. Interestingly, a quantitative relationship between the diffusion coefficient of the drug and the plasticizer level could be established. Based on these results, the release kinetics of diffusion-controlled drug delivery systems could be predicted. In this study, the release patterns from microparticles were calculated and the significant effect of the composition of the device on the resulting release rate was simulated. The latter could be effectively modified by varying the type and amount of plasticizer. Independent experiments verified the theoretical predictions. The practical benefit of the presented method is to calculate the required composition of diffusion-controlled drug delivery systems (monolithic solutions) to achieve desired release profiles.

Transdermal Dual-Controlled Delivery of Testosterone and Estradiol: (I) Impact of system Design

AbstractA multilaminate-type transdermal drug delivery (m-TDD) system was designed with the objective of delivering testosterone and estradiol simultaneously but at different daily dosage rates. To achieve such a dual-controlled transdermal delivery, skin permeation enhancer and permselective membrane were incorporated into the system. The results demonstrated that skin permeation enhancer, which is incorporated into the testosterone reservoir layer, and permselective membrane, which is added onto the drugreleasing surface of estradiol reservoir layer, can both alter the overall rate of skin permeation for both drugs. The skin permeation enhancer was observed to enhance the skin permeation rate of testosterone, while the permselective membrane was shown to reduce the skin permeation rate of estradiol. The addition of permselective membrane was observed to modify the release kinetics of estradiol from the matrix diffusion-controlled drug delivery to membrane permeation-controlled drug delivery. Other facto...