Cirrus Pharmaceuticals, Inc.
Cirrus Pharmaceuticals, Inc.
Headquarters
Durham, NC
Location(s)
Durham, NC
Years in Drug Formulation
12 Years
Spokesperson
Murali Duvvari, Research Scientist II
| Areas of research | |||||||
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Small Molecule |
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Biological |
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Other | ||
| Drug Formulation Services Offered | ||||
| • | Analytical method development | • | Bioavailability enhancement | |
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Compatibility studies of active ingredients |
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Dosage form selection | |
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Excipient compatibility |
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Formulation optimization | |
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Formulation stress testing |
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in silico studies | |
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Manufacture of clinical supplies |
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Novel delivery system | |
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Packaging compatibility assessment |
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Particle size reduction | |
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Preclinical studies |
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Solubilizing water-insoluble drugs | |
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Stability studies |
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Taste masking/flavorings | |
| Other Services Offered | ||||
| Disease Research | Target Identification | |||
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Lead Identification |
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Early Safety Tests | |
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Lead Optimization |
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Pre-clinical Studies | |
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IND Submission |
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Clinical Trials | |
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NDA Submission |
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Post-marketing Studies | |
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| Types of Drugs | |||||||
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Generics |
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Prescription |
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OTC | ||
| Dosage Forms | ||||
| • | Capsules | Implantable | ||
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Inhalation |
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Injectible | |
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Oral |
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Parenteral | |
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Peptide and Protein |
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Tablets | |
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Topical |
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Company’s role in drug discovery and developmnet
Cirrus Pharmaceuticals, Inc. is a Contract Research Organization specializing in Strategic Product Development. Our areas expertises are in Analytical Methods Development/Validation, Preformulation, Formulation Development, Device Selection, and Evaluation, Release, and Long-term stability testing. Cirrus offers a full range of services starting from lead selection through drug product commercialization and can assist with the selection of clinical/commercial manufacturers.
Company’s experience and expertise in drug formulation
Successful formulations have been developed for several small and macromolecules at Cirrus over the past twelve years. Cirrus’s lead formulation scientists have an average relevant experience of about 10-12 years. We have expertise developing formulations for various dosage forms and routes of administration including inhalation, nasal, oral, parenteral, topical/transdermal, buccal, and ocular.
At Cirrus we recognize the fact that each drug molecule is unique and a single strategy (i.e. platform technologies) may not be applicable to the variety of drugs discovered everyday. Cirrus prides in providing value by developing innovative solutions for drug molecules using scientific principles in conjunction with conventional formulation approaches such as solutions, suspensions, emulsions, dry powders, inclusion complexes, complexation/chelation etc. When appropriate, specialized approaches such as nanotechnology are also employed.
Relationship with pharma companies
The intended route of administration sets the limits on potential types of formulations that can be explored and their tolerated characteristics. Based on the route of administration, a given drug molecule is adequately characterized for physico-chemical properties as appropriate. These properties dictate dosage form design, selection of excipients, and formulation process steps. Additional characteristics that are desired in the final drug product (e.g. increased residence time) are also incorporated during formulation development. Cirrus’s formulation team is comprised of experts in the preformulation area specializing in both solution state and solid state characterizations.
Cirrus’s relationship with Pharma companies is purely contractual. We are a strictly fee for service company.
Factors critical for drug formulation
Cirrus’s formulation efforts are mainly focused on target dose of drug in the formulation, physical and chemical stability of formulation, ease of scale up and commercial manufacture, patient compliance (e.g. palatability), regulatory approvability, and cost of manufacture. Other critical factors depend on the mechanism of action (e.g. systemic/local effect) and potential in vivo disposition of the drug molecule (e.g. factors affecting bioavailability).
Cirrus’s scientists employ a systematic approach. The initial efforts are focused on drug dose and stability in a given formulation assisted by preformulation studies. Additional characteristics are included through excipient selection, dosage form design, and optimization of the formulation process. Formulation development is an iterative process; results from formulation characterization studies, stability/compatibility studies, and in vivo evaluations provide feedback for formulation optimization. Our formulation development activities are often aided by Statistical Design of Experiments (DOE). Whenever possible, GRAS excipients are used.
Scientific/business/regulatory trends impacting drug formulation
Current drug discovery approaches through combinatorial chemistry and high throughput screening are geared towards identifying drug molecules with greatest affinity to potential physiological targets. However, many of the candidates identified have poor pharmaceutical properties (e.g. low solubility), necessitating creative formulation solutions. In addition, a significant increase in our understanding of diseases at the genetic level has led to the discovery of new classes drug biomolecules with unique mechanisms of action and formulation requirements to maintain drug effectiveness. A general increase in health awareness by the population and new ways of treating existing conditions have led to a significant need for the development of formulations using alternative routes of administration (e.g. nasal, transdermal) over conventional routes.
One important trend is the promotion by the FDA and ICH of the Quality by Design (QbD) approach to drug development. QbD is a risk-based, systematic approach for gaining understanding of a drug product during its development cycle and ensuring a pre-defined product quality. Statistical design of experiments, which has always been a part of the Cirrus approach, is used in QbD to define a design space to understand critical quality attributes and their variability. In theory, the QbD approach offers a regulatory advantage, in that a change within the design space would not require a post-approval regulatory change process.
As many important patents expire and public demand for lower healthcare costs rise, we can expect to see a significant increase in competitive pressure by generic drug manufacturers.
Success story
A development program for an MDI was initiated for Sepracor in 1999, and a New Drug Application (NDA) was submitted for the product in 2004. The product, Xopenex HFA(R), received regulatory approval in 2005 in the shortest FDA review cycle for an HFA MDI to date. Cirrus’s contributions to that program included preformulation/salt screen, development of the HFA formulation, selection of components, and development, scale-up and technical transfer of the manufacturing process.
How will roles of CROs and contract manufacturers change over the next few years?
The CRO/CMO space within the pharmaceutical/biotech industry has seen an expansion over the past few years and the trend is expected to continue as more small companies, specifically biotechs, with limited development capabilities emerge. As the market becomes more competitive it is imperative that each CRO/CMO establish a niche to survive.
Filed Under: Drug Discovery
