ABSTRACT
Nanosuspension ................................................................................ 312 9.6.2 Establishment of TPP ....................................................................... 312 9.6.3 Proposed Formulation and Manufacturing Process ......................... 312
9.6.3.1 Nanosuspensions as Formulation Strategy ........................ 314 9.6.3.2 High-Pressure Homogenisation as Manufacturing Process ... 314
9.6.4 Identification of CQAs Based on TPP and Proposed Manufacturing Process ..................................................................... 314
9.6.5 Experimental Work ........................................................................... 315 9.6.5.1 Procurement of API ........................................................... 315 9.6.5.2 Selection of Stabiliser and Wetting Agent ......................... 317 9.6.5.3 Optimisation of the Premilling Process Step Using
Ultra-Turrax ....................................................................... 318 9.6.6 Risk Assessment ............................................................................... 319
9.6.6.1 Initial Risk Assessment for Formulation of the Nanosuspension by HPH ......................................... 319
of the Nanosuspension and Their Justification .................. 323
9.6.6.3 Risk Assessment for Lyophilisation Process ..................... 323 9.6.6.4 Updated Risk Assessment for Lyophilisation
of the Nanosuspension and Their Justification .................. 326 9.6.7 Container and Closure System ......................................................... 326 9.6.8 Control Strategy for Manufacturing of the Atovaquone
Nanosuspension ................................................................................ 328 9.7 Inhalation ...................................................................................................... 328
9.7.1 Case Study – Respimat® Soft Mist Inhaler ....................................... 331 9.7.2 The Concept of a Soft Mist Inhaler .................................................. 331 9.7.3 Prototype Development and Demonstration of the Concept
of Providing Mechanical Energy ...................................................... 333 9.7.4 Development of an Easy-to-Use Model ............................................ 333 9.7.5 Introduction of the ‘Uniblock’ Nozzle .............................................. 335 9.7.6 Optimisation of the Mechanical Strength of the Uniblock............... 335 9.7.7 Refinement of Developed Model ...................................................... 335 9.7.8 Working of Respimat ........................................................................ 335 9.7.9 In Vitro Testing ................................................................................. 336 9.7.10 In Vivo Testing ................................................................................. 336 9.7.11 Confirmatory Studies on Dose Reduction via Respimat SMI .......... 337
9.8 Ophthalmic ................................................................................................... 339 9.8.1 Case Study – Cyclosporine Ophthalmic Emulsion ..........................340 9.8.2 Elements of Pharmaceutical Development .......................................340
