New excipients for improving solubility

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Nick DiFranco, Global Market Segment Manager for Oral Treatments, and Joey Glassco, Senior Global Market Manager for Parenteral Drug Delivery, colleagues at Lubrizol Life Science Health, explore the use of amorphous solid dispersions and polymeric micelles to improve solubility.

Between 40 and 70% of marketed drugs and up to 90% of all registered New Chemical Entities (NCEs) suffer from low water solubility. This can have significant negative consequences on the bioavailability of the active pharmaceutical ingredient (API) and potentially impact its therapeutic effect.

The Biopharmaceutical Classification System (BCS) is widely used in the pharmaceutical industry to classify APIs based on their solubility and permeability. It divides molecules into four distinct classes based on their behavior when interacting with water.

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Figure 1

Class II and IV BCS molecules are particularly challenging when it comes to drug formulation, as they require enhanced solubility and/or permeability to provide therapeutic effect.

Different techniques to overcome solubility challenges

A variety of techniques can be used to help overcome drug solubility issues, depending on the unique characteristics of the API in question, as well as the specifics of the formulation and dosage form. These include in particular the following:

  • Chemical modification of API
  • encapsulation
  • Inclusion complexes
  • Physical modification and dispersion of the API.

A number of these sparingly soluble drug formulation techniques are facilitated by excipients. In this article, we will explore the use of amorphous solid dispersions and polymeric micelles for solubility enhancement.

Excipients in action

Amorphous solid dispersions (ASD) or micellar solubilization have been used for decades as tools for improving pharmaceutical solubility and bioavailability (see Table 1). These techniques enhance the solubility of hydrophobic APIs by maintaining drug particles in an amorphous state (i.e., ASDs) or solubilizing the API in the micellar structure, respectively.

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Table 1: Commercial pharmaceuticals using solubility enhancement.

Approach #1: Amorphous Solid Dispersions

Preparation methods for forming ASDs include hot extrusion and solvent evaporation processes, such as spray drying.

Pharmaceutical spray drying is a continuous process in which a liquid feed of API, polymer and solvent is atomized, dried and collected as solid particles.

When selecting excipients for spray drying, several factors must be considered, including solubility in common pharmaceutical solvents, viscosity of the polymer in solution, and ability to stabilize a large amount of drug in an amorphous form. .

Apinovex™ polymers: enabling highly efficient amorphous solid dispersions

Lubrizol’s Apinovex™ Polymers are high molecular weight polyacrylic acid excipients designed to provide both processing and formulation advantages for spray-dried amorphous solid dispersions. Apinovex polymers enable formulators to improve the solubility of Class II and IV BCS APIs and develop more effective oral dosage forms.

The advantages of the Apinovex polymer formulation include:

  • High drug loading (up to 80%) via spray drying
  • Significantly improved dissolution compared to crystalline API
  • Stable amorphous solid dispersions even after six months under accelerated conditions
  • Enables IP protection and lifecycle management/505(b)(2) formulations
  • A high glass transition temperature ensures the stability of ASD.

Processing benefits of Apinovex polymers include:

  • Designed for standard spray-drying and solvent-based processing techniques
  • Soluble in water and common pharmaceutical solvents
  • Produces low viscosity solutions for ease of processing.

Apinovex polymers are safe and compatible with a wide range of APIs. The polymer was commercially manufactured under IPEC-GMP guidelines and samples are available.

Approach #2: Injectable formulations based on polymeric micelles

Low solubility is also a major obstacle for injectable formulations. Micelles have been used in several commercial pharmaceutical products to encapsulate and solubilize APIs for injection.

Amphiphilic block copolymers, which have a hydrophilic head and a hydrophobic tail, possess the ability to self-assemble and generate micellar structures with solubilization properties. Polymer micelles also have a better safety profile compared to small molecule surfactants.

Apisolex™ polymers: increase solubility up to 50,000 times where others fail

Apisolex polymer is a versatile, efficient and safe excipient technology utilizing a poly(amino acid) architecture to overcome the pitfalls of existing technologies. Apisolex technology enjoys strong patent protection, both in the United States and abroad, which enables applications with new chemical entities and new pharmaceutical products entering the market through the 505(b) regulatory pathway. )(2) from the United States Food and Drug Administration (FDA).

Amorphous and highly crystalline hydrophobic APIs can be formulated using Apisolex technology. It decreases the amount of excipient needed to solubilize a hydrophobic API compared to alternative excipients on the market, including Captisol® and other cyclodextrins, enabling the efficient development of next-generation parenteral products.

The amphiphilic poly (amino acid) architecture of Apisolex excipient is comprised of building blocks that occur naturally in the body, resulting in a non-toxic, non-immunogenic, biocompatible and biodegradable alternative to PEG and other other common solubility enhancers. The excipient is manufactured under Good Manufacturing Practices (GMP) and is ready for use in the manufacture of clinical and commercial pharmaceutical products.

Apisolex technology is an ideal option for parenteral drug development projects where traditional excipients or other formulation techniques have failed or where patent-protected technology is desired.

Request a sample today

LLS Health is committed to ensuring the availability of effective and reliable excipients to address solubility issues in oral and injectable formulations. If you are looking for solubility enhancement options, contact our team below:

Request a sample of Apinovex™ Oral Grade Polymer

Request an Injection Grade Apisolex™ Polymer Sample

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