Nowadays, emphasis is being laid to development of controlled release dosage forms. Interest in this technology has increased steadily over the past few years. Although oral administration of drugs is a widely accepted route of drug delivery, bioavailability of drug often varies as a result of gastrointestinal absorption, degradation by first-pass effect, and hostile environment of gastrointestinal tract. Transdermal administration for percutaneous absorption of drug is limited by the impermeable nature of the stratum corneum. Ocular and nasal delivery is also unfavorable because of degradation by enzymes present in eye tissues and nasal mucosa. Hence, the parenteral route is the most viable approach in such cases. Of the various ways of achieving long-term parenteral drug delivery, biodegradable microspheres are one of the better means of controlling the release of drug over a long time. Because of the lipidic nature of liposomes, problems such as limited physical stability and difficulty of freeze-drying are encountered. Similarly, for emulsions, stability on long-term basis and in suspensions, rheological changes during filling, injecting, and storage poses limitation. Also, in all these systems, the release rate cannot be tailored to the needs of the patient. Parenteral controlled-release formulations based on biodegradable microspheres can overcome these problems and can control the release of drug over a predetermined time span, usually in the order of days to weeks to months. Various FDA-approved controlled-release parenteral formulations based on these biodegradable microspheres are available on the market, including Lupron Depot Nutropin Depot and Zoladex. This review covers various molecules encapsulated in biodegradable microspheres for parenteral delivery.
"In recent years there has been an increase in the availability and development of protein and peptide controlled release therapeutics, such as microspheres for sustained perenteral delivery     . Applications of such systems include vaccination [2,6–8] and drug delivery     , for periods of up to 6 months. Understanding the surface and the bulk chemical composition of such microspheres can provide significant insight into the production process and may also contribute to an understanding of the involvement of micro and nanostructure in drug release. "
[Show abstract][Hide abstract] ABSTRACT: Polymer microspheres for controlled release of therapeutic protein from within an implantable scaffold were produced and analysed using complimentary techniques to probe the surface and bulk chemistry of the microspheres. Time of Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) surface analysis revealed a thin discontinuous film of polyvinyl alcohol (PVA) surfactant (circa 4.5nm thick) at the surface which was readily removed under sputtering with C(60). Atomic Force Microscopy (AFM) imaging of microspheres before and after sputtering confirmed that the PVA layer was removed after sputtering revealing poly(lactic-co-glycolic) acid(PLGA). Scanning electron microscopy showed the spheres to be smooth with some shallow and generally circular depressions, often with pores in their central region. The occurrence of the protein at the surface was limited to areas surrounding these surface pores. This surface protein distribution is believed to be related to a burst release of the protein on dissolution. Analysis of the bulk properties of the microspheres by confocal Raman mapping revealed the 3D distribution of the protein showing large voids within the pores. Protein was found to be adsorbed at the interface with the PLGA oil phase following deposition on evaporation of the solvent. Protein was also observed concentrated within pores measuring approximately 2μm across. The presence of protein in large voids and concentrated pores was further scrutinised by ToF-SIMS of sectioned microspheres. This paper demonstrates that important information for optimisation of such complex bioformulations, including an understanding of the release profile can be revealed by complementary surface and bulk analysis allowing optimisation of the therapeutic effect of such formulations.
[Show abstract][Hide abstract] ABSTRACT: Post partum haemorrhage is one of the leading causes of maternal mortality in both the developed and developing world [1,2]. Post partum haemorrhage is caused by the loss of blood from the uterus following labour because of decreased uterine tone, retained placenta or placental fragments as well as lower genital tract trauma . Routine management of post partum haemorrhage involves the use of parenteral oxytocin (OT) that is administered via the intramuscular or intravenous route to increase uterine tone and reduce bleeding. However, OT is rapidly metabolised in the liver and cleared from the body via the kidney . The use of a long acting parenteral preparation of OT to maintain uterine tone is therefore proposed as a means of reducing maternal mortality by preventing post partum haemorrhage. A variety of alternatives were investigated for the development of an appropriate dosage form for OT delivery. The use of Pluronic® F127 (PF-127) as a thermo-sensitive gel that exists as a viscous flowing liquid at low temperatures but forms a stiff gel on warming to body temperature is proposed. The properties of PF-127 allow for the administration of a cold liquid preparation via a syringe and needle into muscle tissue followed by the formation of a depot gel that has the potential for sustained delivery of OT in vivo. Aqueous solutions of PF-127 were prepared using the cold method. PF-127 solutions were characterised with respect to critical micelle concentration and gelation temperature for different concentrations of gel. The temperature at which gelation occurs was found to be concentration dependent. The rheological properties of solutions of PF-127 were also investigated and a dramatic change in viscosity was found to occur simultaneously with the visual onset of gelation. Due to the lack of compendial guidelines for in vitro release testing of controlled release parenteral preparations, different dissolution methods were evaluated for their potential to discriminate between formulations of different compositions. Tests that were used to assess discriminatory behaviour were ANOVA analysis, the f1 and f2 difference and similarity factors, and Gohel’s Similarity factor, Sd. The discriminatory behaviour was assessed by comparing the in vitro release of OT from 20%, 25%, and 30% w/w PF-127 containing preparations and it was observed that the USP Apparatus 3 showed the greatest potential to discriminate between all formulation compositions tested, compared to other test methods that were evaluated. The method was further optimised for OT per dose unit and to establish whether pH changes affected drug release from these systems. The Korsmeyer-Peppas power law was used to assess the primary mechanism of drug release from the extemporaneously prepared dosage forms tested using different dissolution methods. The values of the release exponent, n, revealed that the mechanism of release of OT from PF- 127 gels is generally a combination of diffusion and swelling controlled release or anomalous release. The extent to which diffusion or swelling impacts on the in vitro release of OT was dependent on the specific dissolution test that was used to evaluate the in vitro release of OT.
[Show abstract][Hide abstract] ABSTRACT: This protocol details a method of fabricating off-wafer, multilayered, asymmetric microparticles from the epoxy-based photosensitive polymer SU-8. Also included are methods for altering the surface properties of SU-8 and introducing functional groups for further covalent coupling reactions. These techniques may be used to create microparticles for applications in drug delivery and tissue engineering. Microparticle design, fabrication and surface modification can be completed in 2 d.
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