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Rheumatoid arthritis (RA) is a musculoskeletal disorders that distresses joints and cartilage and may lead to bone degeneration. Intraarticular administration of the drug directly in joints causes relief but is limited by the half – life of the administered drug. The objective of the present investigation therefore was to prepare Dexmedetomidine HCl containing liposomes which were then loaded in xanthan gum gel for intraarticular administration to prolong the duration of drug release. Liposome formulations were prepared by using various ratio of 1,2-Dierucoyl-sn-glycero-3-phosphatidylcholine, 1,2-Dipalmitoyl-sn-glycero-3-phospho-rac-glycerol and cholesterol using thin film hydration method in a Rota evaporator. The liposomes were evaluated for size distribution, surface charge potential, entrapment efficiency for establishing the levels of formulation components and process parameters. Scanning electron micrographs of the liposomes indicated the spherical topography of the prepared liposomes. The liposomes were then loaded in gel formulated using xanthan gum as the gelling agents. Viscosity and gel strength of the formulation was evaluated by rheometer. In Vitro Dissolution in simulated synovial fluid media indicated that the liposomes in gel could prolong the drug release for a period of 7 days.

Multivesicular liposomes (MVLs) are non-concentric, lipid-based micron-sized spherical particles. The usage of MVL for sustained drug delivery has seen progression over the last decade due to successful clinical and commercial applications. It provides attractive characteristics, such as high encapsulation efficiency, variety of sizes, structural stability, and different choices for the route of administration. Drug molecules are encapsulated in internal aqueous compartments of MVL, separated by lipid bilayer septa to form polyhedral structures. The integrity of these entrapped small molecules, peptides, or proteins is maintained throughout the therapy, thus providing sustained drug release on non-vascular administration. Despite the frequent use of unilamellar liposomes, characterization of MVLs is critical due to different puzzling problems, such as real-time size evaluation, initial burst, and in vivo performance. Moreover, available regulatory guidelines on liposomal drug product development are insufficient to assure ample in vitro-in vivo behavior of MVL. This review hereby highlights the innovations pertaining to development and manufacturing procedures, drug release mechanisms, and characterization techniques. The review also summarizes the applications, challenges, and future perspectives for successfully translating the research concept to a clinically accepted delivery system. Despite the intricacies involved in the development of MVL, establishing steadfast characterization techniques and regulatory paths could pave the way to its extensive clinical use.

An intraarticular, liposphere-based, formulation of Imatinib mesylate for weekly administration was developed. Lipospheres were prepared using double emulsion technique using dierucoyl phosphatidylcholine, 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt), cholesterol, and tricaprylin as lipid phase in dichloromethane in a four-step process. Primary emulsion, formed using a high-pressure homogenizer, was diluted using a secondary aqueous phase in an Inline mixer to form the liposomal dispersion. Nitrogen flushing was done to remove dichloromethane, and the dispersion was finally centrifuged and adjusted for potency. The amount of cholesterol and triglyceride was taken as formulation variables, and speed of homogenization was used as a process variable in the Box-Behnken design while particle size, % drug entrapment, and drug release at the end of 4 h and 5 days were taken as response variables. Multivariate data analysis grouped the variables in two latent variable sets, one based on the speed and the other on the composition of lipospheres. Multiple linear regression analysis was used to generate mathematical model for each response. Constraints were put on the values of responses, as per the requirements of the final product, and the "freedom to operate" design space was located using an overlay plot. The center point batch sufficed all the set criteria, and Monte Carlo simulations on the factor variables indicated a defect rate of 5%. The center point batch was characterized for viscosity, osmolality, pH, drug release, and lipocrit value. The dispersion was charged in a prefilled syringe and studied for stability. The product was found to be stable at 2-8°C over a period of 6 months.

Poly(lactic-co-glycolic) acid (PLGA) is a copolymer of polylactic acid (PLA) and polyglycolic acid (PGA), broadly used for the biomedical applications. In the last few decades, it is proven to be a most successful polymeric vehicle used for drug delivery and therefore approved by various regulatory agencies, namely USFDA and EMA. The commercial and clinical success of PLGA is due to unique characteristics such as biocompatibility, biodegradability, high drug entrapment capacity and surface modification possibilities. Various grades of PLGA provide flexibility among scientists to develop formulations of desired release characteristics. Extensive research done so far has depicted the application of PLGA-based carrier systems (microspheres, implants and nanoparticles) for controlled and targeted delivery of small-molecule drugs, proteins, peptides and monoclonal antibodies and other macromolecules for the treatment of various diseases. Apart from drug delivery, PLGA also proved its application in theranostic purposes where it can be attached to a contrast agent for phototherapy along with chemotherapy.. Despite multiple advantages, the usage of PLGA-based complex systems is restricted due to various limitations such as manufacturing/scale-up issue, insufficient regulatory guidance, the lack of trained manpower and IP-related issues. Considering the potential of this polymer for drug delivery and proven clinical application, it became highly important to strengthen the capabilities for the development and manufacturing of PLGA-based carrier systems. This chapter deals with information and discussion of applications of PLGA from lab to clinic with key highlights on associated challenges.