Inhalation drug R&D platform

• Inhalation preparations can be absorbed quickly, reduce the dosage of the drug, and reduce the adverse reactions of the drug. Inhalation preparations  can be used for local and systemic administration. They can be used in innovative drugs, improved drugs and generic drugs. Inhalation formulations are unique in terms of technology development, review and approval.  It is necessary to consider carefully the technology, quality control, drug delivery device and production of the final product.  Medicilon is expert in the development process and has extensive R&D experience of various inhalation formulations, especially in the fields of DPI, nebulizer and nasal spray.  The R&D team are fully integrated with the requirements of global   policies, regulations and guidelines.

Features and Benefits

• Medicilon is equipped with aerosol inhalation and drug delivery equipment for both small and large animals. Equipment includes clean air generation system, aerosol generation system, real-time monitoring and control system for conventional gases such as temperature and humidity, oxygen, carbon dioxide, real-time sampling system and test product concentration real-time adjustment systems.            Allowing for the simultaneous inhalation administration of more than 30 small animals and 10 large animals.             Fully integrated with Chinese and international regulations and requirements to carry out research work.              38 inhalation projects have been completed, of which 2 have entered the clinic stage. (2 of the formulation inhalation projects entered the clinic stage-Shanghai Novamab and Frontier Biotech)

Experience of Project

• In Pharmacy Formulation:

  Completed projects: 19Projects under research: 8Clinical projects: 2         Service experience：Nasal spray development Nebulizer developmentQuality research of inhalation formulationPrescription optimization of inhalation formulation

  In Non-clinical aspect:

  Completed projects: 19Projects under research: 9Species: mice, rats, guinea pigs, dogs, monkeys       Service experience: PK Toxicological pre-testsStudies of safety evaluationRepeated administration of inhalation

Type of Inhalation Preparations

• Inhalation preparations include several types:
  Dry Powder Inhaler，DPI；Dry Powder Inhaler (DPI) refers to the formulation of solid micronized raw material medication alone or mixed with a suitable carrier, using a special dry powder inhalation device for the patient to inhale the aerosolized medicine to the lungs.Nebulizer；Nebulizer refers to a drug delivery device to administer medication in the form of a mist inhaled into the lungs.Meter Dose Inhaler，MDIA Metered Dose Inhaler (MDI) is a device that delivers a specific amount of medication to the lungs, in the form of burst of aerosolized medicine that is usually self-administered by the patient via inhalation.
  

Inhalation Preparation Quality Study

• In addition to conventional physical and chemicalproperties , the quality of inhaled formulations also includes some special indicatiors:
  Aerodynamic Particle Size Distribution, APSD；Fine Particle Dose，FPD；Delivered-Dose Uniformity, DDUDelivery Rate and Total Product Delivered
• Microparticle Dose (Inhalation Solution)
  

  Research has shown that obvious difference in aerodynamic particle size distribution between different principles and models of nebulizers.

  

  The distribution of homemade and reference formulations were basically the same by using the same nebulizer.
• These studies require the use of proprietary analytical equipment. Medicilon's state-of-the-art equipment can deliver the in vitro evaluation required for various inhalation formulations.
  New Generation Impactor BRS 2100 Breath Simulator from Copley Scientific;Particle Size Analyzer from Sympatec.

Exposure Administraion

• Small animal oral-nasal inhalation exposure systemsDogs oral-nasal inhalation exposure systemMonkeys oral-nasal inhalation exposure systemOther Methods of Inhalation Administration:Intratracheal Instillation, Compressed Nebulizer Inhalation, Nebulizer of Micro air-tube.

Inhalation Drug Safety Evaluation Platform

• Medicilon can deliver a complete set of inhaled drug safety test evaluations, including:
  Pharmacokinetic Tissue distribution testAcute Toxicity 28-day repeated dose toxicity Stimulus testAllergy
  Medicilon has established a complete set of technologies for inhalation administration testing, including:
  Intratracheal atomization administration, oral and nasal exposure administration, etc.;Administration to 5 species of rats, mice, guinea pigs, dogs, and monkeys;56-day long-term administration operations;Long-term administration (4 hours) to meet OECD administration time requirements;Powder and liquid drug aerosol generation system for powder and liquid drug delivery.

Drug inhalation pharmacokinetic and toxicological tests

• During aerosol generation for inhaled drugs, the aerosol concentration, particle size and particle size distribution will fluctuate, so it is necessary to adjust the dose and particle size. During the drug administration process of animals, the aerosol concentration is monitored regularly to assess the dosage. In a cycle of administration, the frequency of detection of the aerosol concentration is very high.
  At the same time, the detection of particle size and particle size distribution is also very important in the inhalation drug toxicity test. Inhalation drugs have very strict requirements on the particle size of the aerosol. Only when the diameter is controlled between 1 and 4 microns can the drug be well absorbed by the lungs.
  Medicilon has significant experience in the research and development of inhaled drugs. Before testing, we will conduct a preliminary exploration of particle size, concentration, and aerosol generation. During testing, aerosol concentration, temperature and humidity, oxygen/carbon dioxide and particle size are assessed regularly. During the experiment, there are many detection/sampling points and the detection frequency is high. The status of the animals under assessment is monitored in real time. After the experiment, the animals will be carefully observed clinically, grossly dissected, and histopathological evaluation of various tissues of the respiratory system is performed.
  Experimental Procedure

  Aerosol concentration detection               Humidity / temperature detection              Oxygen/carbon dioxide detection               Particle size detection

  Experimental Animals

  Real-time detection of animal status            Clinical observation             Anatomy           Histopathological evaluation

PK Case:

• Nebulization inside Air-tube in Rats
  
  Oral-nasal exposure in rats, administered for 48 min
  
  Higher average plasmaconcentrations in trachea and lung tissue for inhaled administration compared to oral administration.
  Monkey Nebulized Inhalation, Monoclonal Antibodies
  
  Medicilon has the ability to perform PK studies of multiple inhalation doses in large animal species.

Toxicity Case:

• Duration of administration
  Rats: up to 240 min per day for 28 daysDogs: up to 240 min per day for 28 days
  Special observation indicators to be considered
  Observation after administration: whether the animal is breathing normally, whether there are symptoms of asthma, cough, asphyxia, allergy, etc., whether there are secretions from the mouth and nose... Anatomy and pathology: visual observation of irritation of the animal's tongue, palate, buccal mucosa, nose, pharynx, larynx, trachea, left and right bronchi, left and right lung lobes, and observation of irritation reactions such as congestion, redness, swelling and necrosis; The above organ tissues were taken for pathological histological examination.
  Oral-nasal Exposure in Rats and Dogs, GLP TOX
  

Service Cases

• 

  Medicilon assisted the inhaled nanobody drug LQ036 getting approved for clinical use

  

  Medicilon assists Palaatu to obtain clinical approval for Class 1 new drug PA9159 for rhinitis

Inquire

FAQs

• What is the definition of inhalation formulation?

  Inhalation formulation refer to formulations in which a drug is delivered to the respiratory tract and/or lungs in the form of a mist through a specific device for local or systemic action.

• What are inhaled liquid formulations and inhaled liquid formulations include?

  Inhalation liquid formulation is a dosage form of oral inhalation formulation, which refers to the liquid formulation for nebulizer, that is, through the nebulizer to produce continuous aerosol solution for inhalation, suspension, etc.

  The main types of Inhalation liquid preparation include:
  • Inhalation solution. • Inhalation suspension. • Inhaled solution(the concentrated solution needs to be diluted before using). • inhalation powder(the sterile drug powder needs to be dissolved before using).

• 所有研究均在同一园区内实验室有序完成，切实保证实验进度和项目沟通的高效性，占据数据获取和评估的行业优越性。