Spray Drying 4.0: Integrating AI, real-time monitoring, and green solvents in pharmaceutical and nutraceutical formulations

This is the advanced approach for development of pharmaceutical product with full range and specified limits of variables during procurements, storage and manufacturing process with a qualification, at desired level of quality within the limits of low and higher values of variables to ensures the Pharmaceutical product Quality by design (QbD) of manufacturing a finished product. The Quality by Design is depicted and a portion of its components recognized and process parameters with quality characteristics are identified for every unit activity. Advantages, openings and steps engaged with Quality by Design of Pharmaceutical items are depicted. The point of the pharmaceutical advancement is to plan a quality item and it’s assembling procedure to reliably convey the proposed execution of the item. Quality can't be tried into items however quality ought to be worked in by outline. It incorporates the Quality target item profile, basic quality traits and key parts of Quality by Design. It likewise gives correlation between item quality by end item testing and item quality by Quality by Design. The establishment of Quality by Design is ICH Guidelines. It depends on the ICH Guidelines Q8 for pharmaceutical improvement, Q9 for quality hazard administration, Q10 for pharmaceutical quality frameworks. It moreover gives utilization of Quality by Design in pharmaceutical improvement and assembling of pharmaceuticals.
 Keywords: Quality by Design, Design Space, Target Product Quality Profile, Critical Quality Attributes

Quality by Design is the most recent quality-related trend in pharmaceutical manufacturing (QbD). This paper discusses Pharmaceutical Quality by Design (QbD) as a way to guarantee high-quality pharmaceuticals. Details about Quality by Design are given in addition to a list of its components. The quality parameters and attributes of each unit operation are unique. Pharmaceutical products can benefit from Quality by Design and the steps that can be taken to implement it. High-quality pharmaceuticals and their manufacturing processes form the core of pharmaceutical R&D. It is impossible to verify the quality of a product because this document includes a breakdown of the product's quality profile and the most important aspects of Quality by Design. Comparing the quality of various products can be done in two ways: through Quality by Design and end-product testing (QbD). Quality by Design is based on the ICH Guidelines. ICH guidelines govern the development of pharmaceuticals and the implementation of quality assurance systems. Pharmaceutical development and production can benefit from Quality by Design (QbD).
 Keywords: Concept & background of QbD, Traditional vs QbD Approach, Key elements, PAT, Challenges, Current & Future perspective.

The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB). A quality by design (QbD) approach was applied to identify and link critical process parameters (CPPs) of the spray drying process to critical quality attributes (CQAs) using risk assessment and design of experiments (DoE), followed by identification of an optimal operating space (OOS). A central composite face-centered design was carried out followed by multiple linear regression analysis. Four CQAs were identified; the mass median aerodynamic diameter (MMAD), the liposome stability (size) during processing, the moisture content and the yield. Five CPPs (drying airflow, feed flow rate, feedstock concentration, atomizing airflow and outlet temperature) were identified and tested in a systematic way. The MMAD and the yield were successfully modeled. For the liposome size stability, the ratio between the size after and before spray drying was modeled successfully. The model for the residual moisture content was poor, although, the moisture content was below 3% in the entire design space. Finally, the OOS was drafted from the constructed models for the spray drying of trehalose stabilized DDA/TDB liposomes. The QbD approach for the spray drying process should include a careful consideration of the quality target product profile. This approach implementing risk assessment and DoE was successfully applied to optimize the spray drying of an inhalable DDA/TDB liposomal adjuvant designed for pulmonary vaccination.

Quality by design (QbD) is an essential part of the modern advance to pharmaceutical quality. Quality has been given an importance by all regulatory body for pharmaceutical products. Quality means customer satisfaction in terms of service, products, and process. QbD is best key to build a quality in all pharmaceutical products. This paper gives idea about the Pharmaceutical Quality by Design (QbD) and describes use of Quality by Design to ensure quality of Pharmaceutical Analysis. Under this concepts of be throughout design and growth of product, it is important to identify desire product performance report Target product profile (TPP), Quality Target product profile (QTPP) and identify critical quality attributes (CQA). To recognize the impact of raw material critical material attributes (CAM), critical process parameters (CPP) on the CQAs and identification and control sources of changeability. USFDA launched a pilot programme in 2005 to permit participating firms a prospect to submit chemistry, manufacturing, and controls (CMC) of NDA information representing application of QbD. QbD has its perspectives to contribute the drug design, development, and manufacture of high-quality drug products. In the present review basic consideration of the QbD approach, its historical background, and regulatory needs are discussed. In detail explanation of elements of QbD i.e. method intent, design of experiment, and risk assessment is given. The foundation of Quality by Design is ICH Guidelines. It is based on the ICH Guidelines Q8 for pharmaceutical development, Q9 for quality risk management, Q10 for pharmaceutical quality systems. It also gives application of Quality by Design in pharmaceutical development and manufacturing of pharmaceuticals. Keywords: Quality by design, Critical Quality Attributes, Pharmaceutical Analysis, Design Of Experiment, Risk Assessment, Regulatory.

Exploiting the potential of bacteriophages for phage therapy is an exciting future prospect. However, in order to be successful, there is a pressing need for the manufacture of safe and efficacious phage drug products to treat patients. Scalable manufacture of phage biologics as a stable solid dry powder form is highly desirable and achievable using the process of spray drying. Spray drying of purified phage suspensions formulated with suitable excipients can be carried out in a single step with high process throughput and at relatively low cost. The resulting phage-containing powders can possess good storage shelf-life. The process allows control over the final phage dose in the powder and production of microparticles suitable for a variety of therapeutic uses. Spray dried powders may include different polymer formulations employing a multitude of different triggers for phage release at the target site including pH, enzymes, virulence factors etc. The activity of the phages in spray dried powders is adversely affected during spray drying due to dessication and thermal stresses which need to be controlled. The choice of polymers, excipients and moisture content of the dry powders affects the material glass transition temperature and the stability of the phages during storage. The storage temperature and storage humidty are important factors affecting the stability of the phages in the dry powders. A quality by design (QbD) approach for phage drug product development needs to identify drug product characteristics that are critical to quality from the patient's perspective and translates them into the critical quality attributes (CQA) of the drug product. The relationship between the phage drug product CQAs and formulation development and spray drying process conditions are discussed in this article.

The purpose of the present study was to investigate the influence of method of preparation of large respirable particles of amikacin sulphate on traits and topography and in-vitro aerosol performance. Large respirable particles of amikacin sulfate (50%w/w) were produced by spray-drying and freeze-drying processes using hydrogenated soyaphosphatidylcholine, L-leucine and Poloxamer 188. Particles exhibited 0.04-0.08 g/cm3 tap densities, 7-20 microm geometric particle size, and 1 to 5 microm of mean aerodynamic diameter. Apart from the morphology and topographical features, spray-dried and freeze-dried particles had marginal difference in their solid-state characteristics. Spray-dried particles were dimpled spherical shape with roundness value close to 1(1.066 +/- 0.028), relatively smooth surface texture and produced greater aerosol dispersion with 20% higher fine particle fraction, 6.92% lower impaction loss and 13% less capsule and device retention than freeze dried particles. Traits and topographical features, such as particle size, polydispersity, elongation ratio, roundness, shape, and degree of surface roughness were found to be influenced significantly by spray-drying process and particles produced by spray-drying process showed better aerosol performance due to these differences.

Comprehensive quality by design approach for stable nanocrystalline drug products

Quality by design (QbD) refers to a new approach to product development that could increase efficiencies, provide regulatory relief and flexibility, and offer important business benefits throughout the product life cycle. QbD is increasingly becoming an important and widely used technique in the pharmaceutical industry. QbD can be considered to be system-based approach to the design, development, and delivery of any product or service to a consumer. It is an approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control. Process parameters and quality attributes are identified for each unit operation. Benefits, opportunities, and steps involved in QbD of pharmaceutical products are described. The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product. Quality cannot be tested into products, but quality should be built in by design. It includes the quality target product profile, critical quality attributes, and key aspects of QbD. It also gives comparison between product quality by end product testing and product quality by QbD. The foundation of QbD is ICH guidelines. Hence, if we identify the cause and effect relationship between the various inputs and responses by carefully designed experiments, we can control the quality of the product by simply controlling the inputs such as raw material specifications or process parameters.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research.

In this work, Sect. 8.1 describes a scale-up methodology for spray drying processes based on scientific first principles, simulation models, and process characterization techniques. Special attention is given to the selection of right scale of spray dryer for any given processes and product demands, and also to the ancillary equipment. The main concerns and challenges involved in the establishment of an industrial process are discussed and exemplified with real-case examples. Several modeling tools are introduced and their usefulness and relevance in different stages of process development, viz. product and process familiarization, scale-up trials, and process intensification, are exemplified. The benefits of this methodology and of the mechanistic description during process development are also discussed. Section 8.2 illustrates a case study consisting in the development of a spray-dried dispersion process for a late-stage candidate. The spray drying process was developed under a quality by design (QbD) approach at a large commercial-scale unit. The goal of this section is to highlight some important stages of the methodology (risk assessment, statistical and mechanistic modeling, and design space analysis and verification), emphasizing the benefits and the challenges that can emerge when processes are developed under QbD.

Pharmaceutical has vast areas of formulation and development which design different formulations for different disease conditions and their treatment. Each product developed in the pharmaceutical has to pass the standard prescribed in the monographs. QbD plays an important role in drug product development that is very important because it ensures the stability, safety, and quality of the product. The product quality should be best so that it has per patient compliance. QbD ensures all the safety procedures in the industries that make the stable and good quality and validate the procedure. It also helps in the design of the product and its procedures. It controls all the manufacturing processes and understanding that develops the best quality product. Its modern approach in the pharmaceuticals which aims to develop and design a quality product using its manufacturing process that is intended to deliver constantly and shows good performance. Quality by Design (QbD) is a methodical approach to drug development that emphasizes comprehending and managing the production process to guarantee constant product quality. Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs) are all identified in this examination, which offers a thorough summary of QbD concepts. It talks about how to optimize pharmaceutical formulations and manufacturing processes by using risk assessment tools, Design of Experiments (DoE), and multivariate analysis. It is emphasized how important regulatory guidelines—like those provided by the International Council for Harmonization (ICH) Q8–Q11—are to maintaining compliance and improving product lifecycle management. Additionally, the study examines how QbD might enhance product effectiveness, lower variability, and speed up regulatory approvals. The difficulties in putting QbD into practice, such as the lack of resources and the complexity of data processing, are also discussed. Insights into the strategic application of QbD to improve pharmaceutical product development and production are the goal of this research.

Optimization of the manufacturing process of a complex amphotericin B liposomal formulation using quality by design approach.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.

In addition to the known therapeutic indications for cannabidiol, its administration by inhalation appears to be of great interest. Indeed, there is evidence of cannabidiol's efficacy in several physiological pathways, suggesting its potential for a wide range of applications for both local and systemic pulmonary administration like cancers. Significant advances in pulmonary drug delivery have led to innovative strategies to address the challenges of increasing the respirable fraction of drugs and standardizing inhalable products. Among different devices, dry powder inhalers offer significant advantages including high stability and ease of use. Particle engineering using techniques such as spray drying is now the focus of research and is expected to improve upon, rather than completely replace, traditional carrier-based formulations. The development of carrier-free powders (without lactose-carrier) is mainly used for medicines with low active ingredient doses, which limits the technology. Previously, we demonstrated the benefits of using a cyclodextrin to obtain deflated spherical-shaped powders by spray drying. In this study the potential of this excipient with a very poorly water-soluble active molecule was investigated. Inhalable cannabidiol powders were developed by spray drying, using the solubility enhancers hydroxypropyl-beta-cyclodextrin and ethanol to optimize cannabidiol water-solubility. Electron microscopy images revealed consistent deflated spherical shapes, while particle size analysis showed low polydispersity and suitable sizes for deep lung deposition (2µm). The selected engineered powders (without ethanol) had very high fine particle fractions (> 60%) due to their deflated surface. Finally, the powder was instantly solubilized leading to drug dissolution, which is important for therapeutic efficacy. In conclusion, this study successfully develops a cannabidiol inhalation powder by particle engineering having suitable aerosolization behavior. Due to the speed of the process and the performance of the finished product, this work opens the door for future studies. It has been shown that active molecules that are only slightly soluble in water can be formulated effectively as a powder for inhalation. Other molecules could be tested and subsequent in vivo studies conducted to demonstrate correlation with these in vitro results.