Formulation and Process Development Articles

Hirudin is a 65-amino acid peptide and the most potent and specific known inhibitor of thrombin (Ki = 0.2 pM). The short elimination half-life of hirudin from the body (1 hour) necessitates the use of a sustained and controlled delivery system.

A proliposome method was used to entrap hirudin in liposomes coated with palmitoyl dextran-coated liposomes and lipid-assemblies. In vitro release studies of hirudin were performed using the lipid systems enclosed in dialysis membranes or deposited in the pores of a vascular graft. The activity of hirudin and released hirudin was measured using a thrombin chromogenic substrate assay.

Leucinostatin-A is a nonapeptide isolated from Paecilomyces marquandii, Paecilomyces lilacinus A257, and Acremonium sp., exerting remarkable phytotoxic, antibacterial (especially against Gram-positive) and antimycotic activities. With the aim to find alternative formulation for in vivo administration, a number of Leucinostatin-A–loaded liposomal formulations have been prepared and characterized. Both large unilamellar vesicles and multilamellar vesicles consisting of synthetic and natural lipids were evaluated. In addition, to determine the nature of peptide-membrane interactions and the stability of liposomes loaded with Leucinostatin-A, a Fourier Transform Infrared Spectroscopy study was performed. The results suggest that the mode of interaction of the peptide is dependent on its concentration, on bilayer fluidity, and on liposome type. Finally, the LD50 of both free and liposome-delivered Leucinostatin-A was determined in mice.

The primary objective of this study was to evaluate the effect of drug loading on the release of leuprolide acetate from an injectable polymeric implant, formed in situ, and efficacy of the released drug in suppressing serum testosterone levels in dogs for at least 90 days. An additional objective was to compare the optimum implant formulation with a commercial microsphere product. Evaluated implant formulations contained 45% w/w 75/25 poly (DL-lactide-co-glycolide) polymer having an intrinsic viscosity of 0.20 dL/g, dissolved in N-methyl-2-pyrrolidone. Irradiated polymer solution was mixed with leuprolide at different drug loads (3%, 4.5%, and 6% w/w) prior to subcutaneous administration to dogs. Dog serum was analyzed for testosterone (RIA) and leuprolide (LC/MS/MS) levels and comparisons within the three implant formulation groups were made. Varying the drug load did not significantly affect the release of leuprolide or efficacy of the implant formulation.

Pharmaceutical scientists have long sought the ability to see inside the solid dosage forms they produce to determine their products’ structural features and to better understand their mode of action. Previous studies have used various techniques for visualizing the internal structure of solid dosage forms, including 1H NMR imaging (1), confocal microscopy (2), and conventional microscopy (optical and electron) combined with mechanical slicing of samples (i.e., microtoming) (3). One drawback of several current techniques is their invasive nature that can destroy the sample and prevent any further testing. Another is the techniques’ limited penetration and resolution. Thus, it is probably fair to say that the ideal experimental approach for the three-dimensional structural imaging of pharmaceutical dosage forms has not yet been realized. X-ray microtomography is a relatively new approach to imaging the internal structure of solid dosage forms.

During the past three years, a consensus has grown regarding the need to achieve a higher level of scientific understanding of pharmaceutical products and processes. The US Food and Drug Administration’s process analytical technology (PAT) guidance and the new GMPs have prompted the creation of dozens of discussion forums about developing and implementing analytical methods, using multivariate analysis, and incorporating information technology into pharmaceutical development and manufacturing.These actions are a desirable step forward. To further advance pharmaceutical product and process understanding and bring it to a level of development that is standard in other industries, a structured plan for long-term development and implementation is needed, followed by realistic resource allocation and the formation of a broad partnership among industry, government, and academia.

I akwood Laboratories is a low-profile, privately owned company with what may soon be some high-profile delivery technology. Concentrating solely on injectables, Oakwood submitted two NDAs this past year for its own products employing its patented CHRONIJECT™ microsphere system. Unlike some other polymer-based technologies, Oakwood’s allows for customization of release profiles as well as duration of delivery. Also unusual is the company’s manufacturing heritage — it was spun out from contract manufacturer Ben Venue Laboratories. Drug Delivery Technology interviewed Tony Pera, Executive Vice President & Chief Commercial Officer to learn more about Oakwood and how his polymer-based microsphere technology for injectables allows custom-designed release profiles for multiple classes of drugs.

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John Sampson ,

Drug Delivery Technology ,Vol 3 No 6 · September 2003 ,

ABSTRACT Purpose: To determine whether sodium fluorescein, budesonide, and celecoxib can be delivered to the retina following subconjunctival administration in the rat. Methods: The solutions of sodium fluorescein, budesonide and celecoxib (75 µg dose) with 5% w/v cyclodextrin were injected subconjunctivally in one eye of the anesthetized male Sprague Dawley rats.

INTRODUCTION A major component of success in orally disintegrating tablets (ODT) is good taste. If the product does not taste good, patients and physicians will find another ODT or other product that does taste good. ODT technology is relatively new to the industry and has had a significant impact on patients of all ages.

INTRODUCTION The application of advanced drug technology for delivery of an active pharmaceutical for weeks to months can be limited by patient and physician acceptance related to ease of administration, reliable kinetic profiles, or product costs. There are currently two major types of biodegradable polymer systems for parenteral drug delivery.