Oral Sustained Release Drug Delivery Research Articles

Development and Characterization of LBG-PVA Interpenetrating Networks Incorporating Gliclazide for Sustained Release

Background: Controlled oral dosage forms have always been preferred for drugs with variable absorption, and short biological half life and frequent dosing. The prime goal with sustained release systems is to maintain uniform therapeutic blood levels for more extended periods of time. Interpenetrating networks (IPNs) have been evidenced as uniform sustained release systems. In the current study, polyvinyl alcohol (PVA) and locust bean gum (LBG) based IPNs were developed for the oral sustained release drug delivery of gliclazide (shows variable absorption). Methods: The IPNs were synthesized by emulsion cross-linking method using glutaraldehyde (GA) as a cross linking agent. Gliclazide is a potential second generation, and short-acting sulfonylurea oral hypoglycemic agent having a short biological half-life (2-4 h), variable absorption and poor oral bioavailability. Various batches of IPNs were formulated by varying LBG: PVA ratio and evaluated for percentage yield, drug entrapment efficiency (DEE), swelling properties and in vitro drug release studies. Further characterizations were done by Fourier Transform Infrared Spectroscopy (FTIR), C13 Solid state NMR, X-Ray diffraction study (XRD), Scanning electron microscopy (SEM), and Differential scanning microscopy (DSC) studies. Results: The percentage yield, drug entrapment and equilibrium swelling were observed to be dependent on PVA-LBG ratio and GA amount. Sustained release of drug was observed in all IPN formulations (approx 59 - 86% in 8 h in various batches) with variable release kinetics. SEM studies revealed the regular structures of IPNs. FTIR, XRD, C13 Solid state NMR and DSC studies proposed that drug was successfully incorporated into the formed IPNs. Conclusion: IPNs of LBG and PVA can be used as a promising carrier with uniform sustained release characteristics.

Gastro-retentive drug delivery system for treatment of Ulcer

Due to the comfort of administration, economical and extensibility in formulation, the most adopted route to the systemic circulation is the oral route regardless of the astounding elevation in the drug delivery. Oral drug delivery is the most comforting method of delivery due to its comforting method of delivery, due to its better solubility, accurate dosage and simpler production. Approximately 90% of the drugs are administered orally of which solid oral dosage form is the most chosen class of medicaments. Conventional dosage forms usually exhibit the serum drug concentration fluctuations and irregularities in drug concentration in the tissues with resultant toxicity, low bioavailability and thus low therapeutic effects. Accordingly, the concept of the oral sustained release drug delivery system has gained popularity in advancement. Sustained release drug deliveries have steady and consistent drug release over longer time duration. Here, if the drug release is consistent over the time duration, it is supposed to be controlled release system, however if the system doesn’t achieve the constant drug release but shows the drug release over the longer duration compared to the conventional system, it is prolonged release systems. These systems are hot in the recent trend as they offer huge designing and adaptability range during formulation

Formulation Optimization of Sustained Release Resinate Microcapsules of Tramadol Hydrochloride by Using 3/2 Factorial Design

The main aim of the present work was to develop the microcapsules of tramadol hydrochloride for the oral sustained release drug delivery. Tramadol hydrochloride a BCS class I drug a centrally acting synthetic analgesic was complexed with Indion 254 ion exchange resin. The microcapsules were prepared by encapsulating the prepared resinates by o/o solvent evaporation technique. In the investigation 32 full factorial design was used to investigate the joint influence of two formulation variable amount of eudragit RS 100 and plasticized PEG 400. The results of multiple linear regression analysis indicated that for obtaining a sustained release drug delivery the optimum concentrations of both the plasticizer and coating solution to be used. The factorial models were used to prepare optimized microcapsules and optimized formulations showed sustained release profiles for the extended period of more than 12 hrs. From the present investigations concluded that resinate microcapsules of highly water soluble drug can provide controlled release of drug for extended period.Key Words: Tramadol hydrochloride, ion exchange resinate, microcapsules, sustained release

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system

Context: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.Objective: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.Materials and methods: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.Results: LSH tablets exhibited dynamic swelling–deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.Discussion: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.Conclusions: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

AN EXPERIMENTAL INVESTIGATION ON SUSTAINED DRUG DELIVERY OF RIBOFLAVIN

The purpose of controlling drug delivery is to achieve more effective therapies while eliminating the potential for both under and over dosing and maintenance of concentration of drug in plasma within therapeutic index is very critical. The conventional Oral drug delivery has limitations and produce wide range of fluctuations of drug concentration in the bloodstream and tissues with consequent undesirable toxicity and poor efficiency and also repetitive dosing and unpredictable absorption. And hence the concept of oral Sustained release drug delivery systems has become prominent, which works on many different mechanisms. This work deals with the development of a sustained drug delivery system using riboflavin as the model drug in an IN-VITRO condition. A drug delivery system is fabricated using Poly Vinyl Alcohol (PVA). The effect of temperature and pH are considered to understand the effectiveness of the system. The results of experimental studies are compared with predictions from mass transfer model and Ritger-Peppas model and are in good agreement

Formulation and evaluation of extended release tablets of Diltiazem hydrochloride

Diltiazem HCl is a calcium ion channel inhibitor. The ability to inhibit the influx of calcium ion present in of cardiac and vascular smooth muscle during membrane depolarization is believed to be its therapeutic effect. It is widely used in the treatment of several types of cardiovascular disorders. For achieving better drug product effectiveness, reliability and safety in the modern pharmaceutical design and intensive research, controlled release and extended release drug delivery has become standards. The largest share of drug delivery systems i.e. upto 80% of all the medication accounts to the OSRDD (Oral Sustained Release Drug Delivery). Extended releases tablets of diltiazem HCL was formulated using Hydroxypropyl methylcellulose (HPMC 643) and povidone in different ratios, the extended release behaviour of fabricated tablets were then evaluated. Extended release diltiazem HCL tablets were composed by direct compression method. Formulation was optimized on the basis of different tablet properties and drug release pattern in In-vitro release profile. The resulting formulation produced tablets with required hardness, weight uniformity and friability. The result of In-vitro dissolution study showed that formulation F4 is most appropriate formulation as it exhibits drug release pattern for much longer period of time. A decrease in drug release profile of the drug was observed on increasing polymer ratio.

Formulation and evaluation of Etodolac alginate beads prepared by ionotropic gelation for sustained release

Oral sustained release drug delivery system is getting greater attention due to its therapeutic advantages. Etodolac is a non-steroidal anti-inflammatory drug with potent analgesic and anti-arthritic properties. It has a short biological half life of 6.4 hours and is administered in a dose of 200-400 mg every 6-8 hours. In the present study, a suitable particulate system of Etodolac has been developed, by ionotropic gelation method for sustained release that would result in prolonged clinical efficacy, reduced frequency of administration and lesser side effects. Microbeads were prepared with and without using maize starch as polymer and were evaluated for particle size and size distribution analysis, flow properties, loose surface crystal study, entrapment efficiency, swelling ratio, percentage yield and drug content uniformity and invitro drug release. It was found that the particle size distribution of both formulations was varied within a narrow size range. Drug leaching (15.46 % ± 0.118) was more with presence of maize starch. Entrapment efficiency was retarded with the presence of maize starch. Swelling ratio (54.29 ± 0.151) suggested that maize starch incorporated microbeads swelled more to behave as a matrix for controlled drug delivery. Formation of highly viscous dispersion with the incorporation of polymer led to high percentage yield (51.48% ± 0.180). Drug release data was fitted into various kinetic models and indicated that the mechanism was according to Peppas model. The study revealed that the microbeads of Etodolac could be successfully prepared by ionotropic gelation technique with sustained release characteristics.

ORGANOCLAY PLURONIC F68 – MONTMORILLONITE, AS A SUSTAINED RELEASE DRUG DELIVERY VEHICLE FOR PROPRANOLOL HYDROCHLORIDE

Normal 0 Short half life of Propranolol Hydrochloride (PPN), an antihypertensive drug is a prime requirement to develop a formulation which could sustained the release of PPN in the human body and also eliminate daily multiple dosage of Propranolol. In this study organoclay Pluronic F68 modified Montmorillonite (Mt) has been explored as a sustained release carrier for oral delivery of PPN. The developed organoclay PF68-Mt was compared for adsorption capacity of PPN with pristine Mt. A detailed and systematic study to evaluate t he effect of pH, time and initial PPN concentration on drug loading capacity of organoclay PF68-Mt and pristine Mt has been evaluated. The synthesized PF68-Mt-PPN composites were characterized by XRD, FTIR, TGA techniques. XRD studies suggested the intercalation of PPN within the pristine Mt and organoclay PF68 - Mt. In vitro drug release profile of PPN from organoclay PF68-Mt composites is compared with that of Pristine Mt and the pure PPN, in simulated gastric and intestinal fluids. The release profile of loaded PPN in organoclay PF68-Mt shows pH dependent release in simulated gastrointestinal fluid. The release behaviour of PPN from PF68-Mt-PPN composites was appeared to be in more sustained manner than prisine Mt and pure PPN over a period of 24 hours. This study suggests that the modification of Mt with a non ionic tri block co polymer Pluronic F68 provides better controlled on the release of PPN as compared to pristine Mt and pure drug. The obtained PF68-Mt-PPN composites with high drug loading capacity and sustained drug release characteristics supposed to be a better oral drug delivery system, for a highly hydrophilic low molecular weight antihypertensive drug PPN. The PF68-Mt-PPN composites developed have the potential to minimize the drug dosing frequency and hence improving the patient compliance. Thus, proposing a new promising formulation for oral sustained release drug delivery.

In vitro and In vivo Characterization of Pectin Based In situ Gelling System of Famotidine

In this study famotidine was used as a model drug to formulate and evaluate pH-induced in situ gelling system for oral sustained release drug delivery in stomach which has shorter biological half-life. To study the effect of independent variables 32 full factorial design was employed, concentration of pectin as pH dependant polymer and concentration of calcium chloride on dependent variables like viscosity, drug content, 50% and 80% drug release and similarity factor. It was found that both the concentration of pectin and concentration of calcium chloride had significant effect on viscosity, drug content, 50% and 80% drug release and similarity factor of the system. In vitro drug release study showed that drug released from the in situ gel followed non-Fickian diffusion. Mathematical modeling was employed for quantitative evaluation of the effect of formulation variables. Rat pylorus legation model was used for in vivo study of the selected formulation. Results shows gel formation in gastric juice and reduction in ulcer index. There were few or no major changes in the formulation during three months stability testing. The in situ gelling systems are useful for delivery of famotidine.

FORMULATION AND EVALUATION OF MATRIX DIFFUSION CONTROLLED TRANSDERMAL DRUG DELIVERY SYSTEM OF GLIPIZIDE

Context: There has been a tremendous increase in interest for transdermal drug delivery system for sustain release dosage form in chronic manageable diseased conditions like diabetes, hypertension etc to reduce the frequency of dosing. It reduces the risk of exposing the body to drug above maximum safe concentration in case of dosage form failure in comparison to oral sustained release drug delivery system. Aims: Transdermal patches of Glipizide were formulated to achieve sustain release pattern within the therapeutic range. Methods and Material: HPMC 5cps, HPMC 15cps, HPMC K-100M, Ethyl cellulose (EC), Eudragit RS 100 (ERS-100) and Polyvinylpyrrolidone (PVP) K30 were used as matrix forming polymer. Propylene glycol was used as penetration enhancer. Polyethylene glycol (PEG) 400 and n-dibultyl phthalate (n-DB) were used as plasticizer. Methanol and chloroform were used as solvents. Patches were prepared by solvent casting method. Results: Patches prepared, from each batch, gave release profile for over 10 hours. Conclusions: Prepared patches from HPMC 5 cps and ethyl cellulose exhibited good characteristics for sustained release action and other parameters evaluated.

Investigation of synthetic spermaceti wax as a potential oral sustained release drug delivery system

The present study was aimed at investigating drug release from spermaceti wax matrices. Materials such as ethylcellulose and methylcellulose were incorporated into the spermaceti wax matrices and release was evaluated. Spermaceti wax can form matrices that release drug in a sustained release fashion. Higuchi or first order release kinetics were found to explain drug release from spermaceti wax, spermaceti wax-ethylcellulose and spermaceti wax-methylcellulose matrices. However, ethylcellulose and methylcellulose enhanced release rate from spermaceti wax matrices. Spermaceti wax matrices can be used to provide drug delivery systems with prolonged action. Release rate from such systems can be regulated by incorporation of materials such as ethylcellulose and methylcellulose. Keywords: carnauba wax, sustained release, particle size, and kinetics East and Central African Journal of Pharmaceutical Sciences Vol. 7 2004: 24-26

Development of an oral sustained release drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer

A new oral sustained-release (SR) drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer (CP) has been proposed. This swelling polymer incorporation layer system, referred to as SPILA system, consists of core granules coated with a mixture of CP, water insoluble polymer, and water-soluble polymer (WP). Release profiles of metoprolol tartrate (ME) from SPILA system were pH dependent: drug release was slower in the medium of pH 1.2 than in the medium of pH 6.8 due to a coating layer with pH-dependent swelling polymer, CP. Lower C max, longer T max, longer MRT and higher AUC values were obtained following administration of SR granules based on SPILA system to beagle dogs compared with pH-independent SR granules having a coating layer without CP, while both SR granules provided similar in vitro release profiles. Moreover, using morphine hydrochloride (MO), in vitro and in vivo performances of the SPILA system were investigated. pH-dependency on the release profiles of MO from SPILA system was more evident when the amount of CP incorporated in SPILA system was increased. AUC and MRT values following administration of SR granules of MO with a coating layer containing 8% of CP to beagle dogs were 191 ng h/mL and 10.6 h respectively, while those following SR granules of MO with a coating layer containing 1% of CP to beagle dogs were 86.4 ng h/mL and 5.86 h, respectively. An important role of CP in the release-regulating layer of SPILA system for keeping the higher and more extended plasma levels of morphine free base was confirmed from the in vivo performance of SPILA system.

The Effect of Processing Variables on the Release of Ibuprofen and Caffeine from Controlled-Release Nonswellable Core-in-Cup Compressed Tablets

An aqueous soluble polymer such as hydroxypropyl methylcellulose (HPMC), which is widely used in oral sustained-release drug delivery systems, swells when it comes into contact with an aqueous environment. In core-in-cup systems the swelling of the HPMC splits open the cup portion of the tablet. This study investigated the use of acacia, tragacanth, polyethylene glycol 6ooo (PEG 6ooo), and hydroxyethylcellulose (HEC) as possible alternatives to the use of HPMC to control the release of cageine (soluble) and ibuprofen (insoluble) from core-in-cup compressed tablets. It also investigated the possibility of producing a core-in-cup system that had the ability to release caffeine and ibuprofen for a maximum time of constant release of 8-12 hr. A preliminary study revealed that acacia was most eflective for the release of caffeiinefrom the core-in-cup compressed tablets, and that PEG 6cux) was most effective for the release of ibuprofen from the core-in-cup compressed tablets. On further investigation it was found that by means of adjusting the hardness of compression and the concentration of polymers used, it was possible to formulate a core-in-cup system that could release drug at a constant rate from the core-in-cup compressed tablets for 8 to 12 hr.