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Biovolutions launched several Nanobiotechnology formulation development contracts

June 2009 : Biovolutions launched several Nanobiotechnology formulation development contracts with local and international clients...read more.

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ANALYTICAL SERVICES

Analytical Services evaluates the performance of the formulation using various analytical and dissolution testing procedure enabling foundation for future developments.

BioVolutions Inc. develops and qualifies a range of analytical methods for clients or installs and qualifies existing methods to be used for subsequent formulation development or stability testing activities. Our strong background in analytical chemistry allows us to produce efficient, quality data. In addition to developing stability indicating analytical methods, BioVolutions identifies impurities and degradation products from solid API material, as well as formulated product using HPLC/MS/MS.

BioVolutions develops appropriate methods to characterize small molecule using a variety of solid phase techniques, as well as for proteins, including molecular weight determination and peptide mapping.

Service

Description

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HPLC Testing

A type of column chromatography used to identify, quantify and separate chemical compounds.

A substance of interest, dissolved in the mobile phase, is pumped through a chromatographic column packed with the stationary phase. The elutant is analyzed by a detector upon exiting the column. Depending on the interactions between the stationary phase, the molecules being analyzed, and the solvent(s) used, the elution/retention time for different molecules will vary allowing for identification, quantification and separation of these molecules.

Particle Size Analysis

An automated laser diffraction analysis instrument used for measuring the size of particles in low-turbidity media (emulsions, suspensions and powders).

Its basic principle is based on the diffraction and diffusion of a laser beam passing through a volume which contains particles. As the beam passes through, the light is scattered at angles that are inversely proportional to the size of the particles. The scattered light is interpreted by a series of detectors as a map of angular intensities, which is then used to calculate the particle size.

Drug Dissolution/In Vitro Release

An automated dissolution test for measuring the release of the drug substance from the drug product.

Drug absorption from a solid dosage form (tablet, capsule) after oral administration or semisolid form after topical administration is profiled by measuring the dissolution of the drug substance in physiological media. 

 

Dissolution Testing

The dissolution properties of a drug determine its release profile to match the product specifications. All new drugs should meet current USP dissolution test requirements, Dissolution Testing should be performed in GLP-compliant laboratory.

BioVolutions measures drug dissolution for both oral as well as topical formulations. For oral formulations, below saturation at 37ºC in water or aqueous based buffers (pH range of 1 to 7) in a dissolution apparatus under precisely controlled mechanical and operational parameters. Depending on the nature of the drug (and in accordance with a developed and validated protocol) the tests are conducted for various durations from 15 minutes to 24 hours with appropriate sampling. The results of the dissolution analysis are reported as cumulated percent drug dissolved at specified time intervals. For topical formulations, BioVolutions employs an in-line In Vitro Release apparatus to measure drug dissolution, especially for SUPAC for manufacturing compliance.

BioVolutions’ drug dissolution studies are performed in a GLP-compliant lab.
Drug absorption from a solid dosage form (tablet, capsule) after oral administration or semisolid form after topical administration depends on:

  • the release of the drug substance from the drug product
  • the dissolution or solubilization of the drug under physiological conditions
  • the permeability across the gastrointestinal tract  or the epidermal membrane

Because of the critical nature of the first two of these steps, in vitro drug dissolution is predictive of in vivo performance. Based on this general consideration, in vitro drug dissolution tests for immediate-release tablets and capsules and topical gels are used to:

  • guide development of new drug formulations
  • assess the lot-to-lot quality of a drug product

Knowledge of the dissolution properties of a drug should be considered in defining dissolution test specifications for the drug approval process. This knowledge should also be used to ensure continued bioequivalence of the drug, as well as to ensure the drug’s sameness under scale-up and post-approval changes. Acceptable bioequivalence and comparable in vitro dissolution data should submitted to the FDA  together with chemistry, manufacturing, and controls (CMC) data to characterize the quality and performance of  the drug are required for FDA approval of  new-drug applications (NDAs) and abbreviated new-drug applications (ANDAs) (21 CFR 314.94). 
For approval, all new drugs should meet current USP dissolution test requirements, if they exist. The approaches for setting dissolution specifications for generic drugs fall into three categories, depending on whether an official compendial test for the drug product exists, and on the nature of the dissolution test employed for the reference listed drug:

  1. USP Drug Product Dissolution Test Available
  2. USP Drug Product Dissolution Test Not Available; Dissolution Test for Reference Listed  NDA Drug Product Not Publicly Available
  3. USP Drug Product Dissolution Test Not Available; Dissolution Test for Reference Listed  NDA Drug Product Publicly Available. In this instance, a dissolution profile at 15-minute intervals of test and reference products (12 units each) using the method approved for the reference listed product is recommended.

The FDA’s Division of Bioequivalence may also request submission of additional drug dissolution testing data as a condition of approval, when scientifically justified.  For further information, see Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), August 1997.

Analytical Method Development

BioVolutions Inc. develops and qualifies many types of analytical methods for its clients and the methods are tailored to project requirements. Typical analytical methods consist of two components: separation and detection.  The majority of analytical methods used at BioVolutions are based on liquid chromatographic separation using common separation techniques.  These include normal and reverse phase chromatography, ion-exchange chromatography and size exclusion chromatography.  Several types of detectors are available such as UV or MS and their use is determined by properties of the analyte.

In addition, BioVolutions offers ELISA method development for biological detection of proteins and peptides.

BioVolutions offers analytical method development and validation which conform to both international and U.S. regulations. At your discretion, our scientists can either work with the data you provide or we can do our own analysis, using a small amount of your reference material.

Stability Indicating Method

A stability indicating method is necessary for a successful drug development program.  BioVolutions develops and qualifies stability indicating methods based on HPLC/UV and HPLC-MS analytical techniques. 

In development of a stability indicating analytical method a separation technique is adapted to resolve the analyte of interest from impurities, degradation products, and excipients.  The most common technique used for this purpose is liquid chromatography.

Following ICH guidelines, Biovolutions will place the API or the product on accelerated stability at 40º C/75%RH for 6 months, medium-term stability at 30º C/65% RH for 9 months and long-term stability at 25º C/60% RH for 2 years.

In addition, since pure samples of degradation products are rarely available, forced degradation studies are undertaken that mimic the degradation/decomposition of the drug substance under a wide range of conditions.

Particle Size Measurements

Particles are measured by laser diffraction technology over a wide size range, from 0.02-2000 mm, accurately and non-destructively, for both wet and dry dispersions. Our methodology broadly follows recommendations outlined in ISO13320-1, the international standard for laser diffusion. In particular, section 6.2.3 (Dispersion) is followed closely. In both wet and dry methods development the objective is to understand the effect of energy on the particulate system (distinguishing conglomerates from dispersed particles) in line with the needs of measurement outcomes (bulk or primary particle size). In a dry measurement, to assess both dispersion and the extent of attrition (if applicable), the material is subjected to what is called a “pressure-size titration” where the effect of increasing controlled energy input is examined (See Section 6.2.3.2 ISO 13320-1). Controlling the DP across the venture regulates this energy input. Shear processes by acceleration will (in theory) separate any agglomerates into primary particles. Increased energy can cause attrition of friable samples especially those that are organic or of high aspect ratio. For large samples then another consideration is that of carrying the particles through the measurement zone in the air stream and high flow rates are normally used for this.

To ensure that we meet the needs of our customers in complying with the requirements of Regulatory Authorities such as the US Food and Drugs Administration (FDA), BioVolutions provides particle size measurements for products subject to FDA regulation, we have solutions to help with 21 CFR Part 11 compliance.

  

Please contact BioVolutions for additional information.

 

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