Gastroretentive Formulations for Improving Oral Bioavailability of Drugs-Focus on Microspheres and their Production

Oral administration is the most commonly used drug delivery route for the majority of conditions. Given its advantages over other routes, such as convenience and cost, its use is increasing every year despite the major advances in drug delivery. Nevertheless, oral formulations are limited and challenged by physicochemical barriers and highly variable residence times. Gastric retention is a strategy that can overcome the highly variable gastric residence time by designing formulations that remain in the stomach longer than would otherwise be expected. This is especially beneficial for drugs that have an absorption window in the stomach and proximal intestine. Various techniques are discussed and include gasgenerating tablets, floating microspheres, hydrodynamically balanced systems, bioadhesive particles, rafts and modified shape systems. Microspheres having the advantages of being multi-unit are further discussed with regard to their production methods and characterisation. Further, a summary of microsphere studies is presented that looks at methods used and key results

Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells

This study aimed at development of poly (lactic-co-glycolic acid) (PLGA) nanoparticles embedded with paclitaxel and coated with hyaluronic acid (HA-PTX-PLGA) to actively target the drug to a triple negative breast cancer cells. Nanoparticles were successfully fabricated using a modified oil-in-water emulsion method. The effect of various formulations parameters on the physicochemical properties of the nanoparticles was investigated. SEM imaging confirmed the spherical shape and nano-scale size of the nanoparticles. A sustained drug release profile was obtained and enhanced PTX cytotoxicity was observed when MDA-MB-231 cells were incubated with the HA-PTX-PLGA formulation compared to cells incubated with the non-HA coated nanoparticles. Moreover, HA-PLGA nanoparticles exhibited improved cellular uptake, based on a possible receptor mediated endocytosis due to interaction of HA with CD44 receptors when compared to non-coated PLGA nanoparticles. The non-haemolytic potential of the nanoparticles indicated the suitability of the developed formulation for intravenous administration

A PLC based power factor controller for a 3-phase induction motor

This paper proposes a power factor controller (PFC) for a three-phase induction motor (IM), utilizing the programmable logic controller (PLC). This work focuses on the implementation of a laboratory model for a PLC based PFC to improve the power factor of a three-phase induction motor. In addition to keep its voltage to frequency ratio constant in order to maintain a maximum torque over the whole control conditions. During the online process a set of capacitors sized in a binary ratio will be switched on or off with the help of zero voltage static switches according to a control strategy to obtain a pre-specified power factor. This control strategy relies on a look-up table and an expert system. The look-up table is prepared according to a measured value of the phase angle between the stator phase voltage and the stator phase current. Implementation of a software algorithm incorporates measuring the power factor angle, selecting the binary pattern according to the control strategy and sending command signals to switch the appropriate capacitors and protection switches. Zero voltage switching of static switches is also allocated in the control algorithm to prevent the occurrence of the transients, pseudo oscillation and harmonics. Experimental studies have been carried-out for verifying the operation performance of the proposed PFC under different operating conditions. Details of the experimental setup and test results in addition to the recommendations are also demonstrate

A programmable SCR-based AC voltage regulator

This paper describes the design, simulation and implementation of a self adjustment programmable AC voltage regulator. The regulator hardware consists of thyristors, a signal conditioner and, an 8-bit microcontroller. The regulator monitors the voltage across a load. The firing angles of the thyristors are automatically adjusted to keep the voltage within the prescribed level independent of the load fluctuations. The regulator was tested for resistive and inductive loads. The results indicate acceptable accuracy levels depending on the control range specified by the user. The regulation range can be from 0-220 V A

Implantable drug delivery systems for the treatment of osteomyelitis

Osteomyelitis is an infection of the bone tissue and bone marrow which is becoming increasingly difficult to treat due to the infection causing pathogens associated. Staphylococcus aureus is one of the main bacteria that causes this infection, which has a broad spectrum of antibiotic resistance making it extremely difficult to treat. Conventional metal implants used in orthopaedic applications often have the drawback of implant induced osteomyelitis as well as the requirement of a second surgery to remove the implant once it is no longer required. Recently, attention has been focused on the design and fabrication of biodegradable implants for the treatment of bone infection. The main benefit of biodegradable implants over polymethylmethacrylate (PMMA) based non-degradable systems is that they do not require a second surgery for removal and so making degradable implants safer and easier to use. The main purpose of a biodegradable implant is to provide the necessary support and conductivity to allow the bone to regenerate whilst themselves degrading at a rate that is compatible with the rate of formation of new bone. They must be highly biocompatible to ensure there is no inflammation or irritation within the surrounding tissue. During this review, the latest research into antibiotic loaded biodegradable implants will be explored. Their benefits and drawbacks will be compared with those non-degradable PMMA beads, which is the stable material used within antibiotic loaded implants. Biodegradable implants most frequently used are based on biodegradable natural and synthetic polymers. Implants can take the form of many different structures; the most commonly fabricated structure is a scaffold. Other structures that will be explored within this review are hydrogels, nanoparticles and surface coatings, all with their own benefits/drawbacks

A programmable SCR-based AC voltage regulator

This paper describes the design, simulation and implementation of a self adjustment programmable AC voltage regulator. The regulator hardware consists of thyristors, a signal conditioner and, an 8-bit microcontroller. The regulator monitors the voltage across a load. The firing angles of the thyristors are automatically adjusted to keep the voltage within the prescribed level independent of the load fluctuations. The regulator was tested for resistive and inductive loads. The results indicate acceptable accuracy levels depending on the control range specified by the user. The regulation range can be from 0-220 V A

Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel

This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above ±30 mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl

Ex vivo and In vivo Evaluation of Chitosan Coated Nanostructured Lipid Carriers for Ocular Delivery of Acyclovir

Background: Herpes keratitis is the most common infectious cause of blindness in the developed world. It may be treated by acyclovir (ACV), however this antiviral drug is poorly soluble with low ocular bioavailability requiring high and frequent dosing. Nanostructured lipid carriers (NLCs) were investigated to improve the ocular bioavailability of ACV by enhancing corneal penetration as well as prolonging the exposure of infected cells to the antiviral agent. Methods: Cell uptake studies, ex vivo tolerance and cell uptake efficacy as well as in vivo corneal permeation of the developed lipid based formulations were investigated. NLCs were fabricated by the hot microemulsion technique and coated with 0.5% w/v chitosan. NLCs were capable of increasing the cell uptake of encapsulated fluorescein and ACV as examined by fluorescence microscopy and high performance liquid chromatography (HPLC) respectively. Results: When entrapped in NLCs, the antiviral efficacy of ACV was increased by 3.5 fold after 24 hrs of exposure. The in vivo corneal permeation of the formulation was studied on Albino rabbits with NLCs capable of increasing the corneal bioavailability by 4.5 fold when compared to a commercially available ACV ophthalmic ointment. Conclusion: NLCs enhanced the ocular bioavailability and antiviral properties of ACV through cell internalisation, sustained release, and increased corneal permeation

Ultrasound-Mediated Ocular Drug Delivery: From Physics and Instrumentation to Future Directions

Drug delivery to the anterior and posterior segments of the eye is impeded by anatomical and physiological barriers. Increasingly, the bioeffects produced by ultrasound are being proven effective for mitigating the impact of these barriers on ocular drug delivery, though there does not appear to be a consensus on the most appropriate system configuration and operating parameters for this application. In this review, the fundamental aspects of ultrasound physics most pertinent to drug delivery are presented; the primary phenomena responsible for increased drug delivery efficacy under ultrasound sonication are discussed; an overview of common ocular drug administration routes and the associated ocular barriers is also given before reviewing the current state of the art of ultrasound-mediated ocular drug delivery and its potential future directions.</jats:p

Development of a stability-indicating UPLC method for determination of isotretinoin in bulk drug

A highly sensitive and rapid stability indicating ultra-performance liquid chromatographic (UPLC) method was developed for the quantification and identification of isotretinoin in bulk. Chromatographic separation was developed using a gradient elution in a reversed-phase system at flow rate of 0.5 ml/min with 12 min run time. The mobile phase was a gradient mixture of mobile phase A (contained a 30:70:0.5 mixture solution of methanol/purified water/glacial acetic acid) and mobile phase B (contained a 70:25:4.5:0.5 mixture solution of methanol/acetonitrile/purified water/glacial acetic acid). Eluents were monitored at 355 nm. The analytical method was validated for accuracy, precision, robustness, linearity, and forced degradation in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) topic Q2 (R1) ‘Validation of Analytical Procedures: Text and Methodology’. The method was linear over a concentration range of (1–7 µg/ml) with correlation coefficient of (r2 > 0.9999). The accuracy was confirmed by calculating the % recovery which was found to be 100.0–101.6%. The RSD values obtained for repeatability and intermediate precision experiments were less than 2%. The limit of detection (LOD) was 0.12 µg/ml, while the limit of quantification (LOQ) was 0.38 µg/ml. The drug samples were exposed to different stressed conditions and the results showed that all degradation products were satisfactorily separated from each other and from the peak of the drug using the developed method. The proposed method can be used for the quantitative determination of isotretinoin with confidence