Potential of Continuous Manufacturing for Liposomal Drug Products.

Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g., improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application.

A Cheap and Convenient Method of Liposome Preparation Using Glass Beads as a Source of Shear Force.

Liposomes, the biocompatible lipid bilayer vesicles, have attracted immense attention due to their distinctive features such as efficient vehicle for the delivery of a wide range of therapeutic agents, adjustable formulation properties, and high drug entrapment efficiency. In this contribution, we present a simple method for the preparation of liposomes using glass beads and compared the potential of this method with conventional methods of liposome preparation. The prepared liposomes were characterized by different analytical techniques (HPLC, DLS, TEM, differential scanning calorimetry, and in vitro drug release). Our findings revealed that the particle size of liposomes is mainly dependent on the size of the glass beads and the glass bead shearing time. An average liposome size of 67.7 ± 25.5 nm was obtained using 2-mm glass beads after 24-h incubation at 200 rpm. The liposomes prepared under the optimized conditions exhibited a high encapsulation efficiency of 92.1 ± 1.7% with 31.08% drug release after 360 min at 37°C. In conclusion, the developed method is a simple and convenient process of liposome preparation of different sizes with desirable entrapment efficiency capacity.

Does Extended-Release Liposomal Bupivacaine Better Control Pain Than Bupivacaine After Total Knee Arthroplasty (TKA)? A Prospective, Randomized Clinical Trial.

Liposomal bupivacaine periarticular injection (PAI) offers sustained bupivacaine release after TKA, but few prospective independent studies exist. In this prospective, blinded study, liposomal bupivacaine was randomized against bupivacaine and incorporated into a comprehensive multimodal pain management protocol. 111 primary TKAs were randomized to receive PAI: 58 patients received 266 mg (20cc) liposomal bupivacaine mixed with 75 mg (30cc) 0.25% bupivacaine, and 53 patients received 150 mg (60cc) 0.25% bupivacaine. Visual analog pain scores and narcotic use were determined. No pain score differences occurred between study and control patients: Day 1: 4.5/4.6 (P=0.73); Day 2: 4.4/4.8 (P=0.27); or Day 3: 3.5/3.7 (P=0.58). Narcotic use was similar during hospitalization, 51.8/54.2 (P=0.34). The study medication costs $285, and the control medication costs $2.80. This finding does not justify the routine use of liposomal bupivacaine.

[Biotechnologic drugs and chemotherapy for infectious diseases]. / Fármacos biotecnológicos y quimioterapia antiinfecciosa.

Developments in biotechnology in recent years have enabled the discovery of new pharmacological agents for the treatment and prophylaxis of infectious diseases. The agents obtained from these biotechnological procedures possess specific characteristics which significantly distinguish them from drugs obtained by chemical synthesis. These properties cover the entire development process, from investigation and production up to their administration to patients. The pharmokinetics of these preparations influence their administration routes and dosage regimens. The discovery of these drugs has led to major advances in the treatment and prophylaxis of infectious processes which until very recently had no effective treatment. The investigation and production of these drugs requires the use of highly technical resources resulting in high costs and therefore a more expensive drug on the market compared to other drugs. Nevertheless, well documented pharmoeconomic studies show that the use of this type of drug for certain symptoms may be highly cost effective. This article includes some of the possible applications of biotechnology in the infectious disease field, although the current situation indicates that more detailed and broader applications may be elaborated on in ensuing issues. The future of these drugs in chemical therapy for the treatment and prophylaxis of infectious diseases is exceedingly promising and many of these drugs are currently under laboratory investigation, more so than those under development from a chemical synthesis approach.

Cost-effectiveness analysis comparing chemotherapy regimens in the treatment of AIDS-related Kaposi's sarcoma in Brazil.

BACKGROUND: Economic analyses of agents used in the treatment of AIDS and opportunistic diseases are particularly important in developing countries. PURPOSE: To analyze the cost-effectiveness of AIDS-related Kaposi's sarcoma (AIDS-KS) chemotherapy regimens in Brazil. METHOD: A decision-analysis model was developed, and effectiveness data were derived from randomized phase III trials evaluating pegylated liposomal doxorubicin (PLD), liposomal daunorubicin (DNX), and the ABV regimen (doxorubicin, bleomycin, and vincristine). Resource data on direct medical costs were obtained from local sources. RESULTS: The cost-effectiveness estimates (defined as average costs per patient who responds completely or partially) favored PLD (US $10,272/responder) in comparison to DNX (US $16,263/responder). Regarding cost-effectiveness, the ABV regimen that is widely used in developing countries had better results when compared to both PLD (US $1,268 vs. US $10,271) and DNX (US $1,268 vs. US $16,260). The incremental cost per additional responder of using PLD instead of ABV was US $20,990. Sensitivity analyses suggest that these results hold over a wide range of assumptions. CONCLUSION: ABV seems to be the most reasonable treatment option for AIDS-KS patients in resource-limited countries like Brazil.

Lipid formulations of amphotericin B.

The incidence of systemic fungal infections, especially in immunocompromised patients, has continued to increase during the past few decades. Treatment with conventional amphotericin B has been the standard care for the majority of patients with invasive fungal infections, despite its associated toxicity. Three lipid formulations of amphotericin B have now been approved for use in the United States. The pharmacology, pharmacokinetics, clinical experience, toxicity, dosing strategies, and cost of these three preparations--amphotericin B lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B--were reviewed in detail in this chapter. The clinical data indicate that lipid formulations of amphotericin B represent an important therapeutic modality in the management of invasive fungal infections.

[Liposomes: promising perspectives]. / Liposomes: des perspectives intéressantes.

NEW THERAPEUTIC VECTORS: Liposomes are nontoxic biodegradable lipid particles which can vehicle drug compounds to the site of action, thus limiting the risk of general toxicity. WITH AMINOGLYCOSIDES: Liposome vectors for aminoglycosides, particularly amikacin, have been developed. Oto- and hepatic toxicity can be limited allowing the use of higher doses for longer periods. WITH AMPHOTERICIN B: Liposomal amphotericin B is now available and appears to give interesting results both in terms of efficacy and tolerance. OTHER APPLICATIONS: Capsular forms of other antibiotics such as ciprofloxacin are being studied. An encapsulated anticytomegalovirus agent, foscamet, is also be explored. In cancerology, liposomes could be developed to deliver toxic agents such as doxorubicin for example. The high cost of these therapeutic vectors does however limit their current use.