Pharmaceutics

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3 pages, 176 KiB

Open AccessEditorial

Aspects and Implementation of Pharmaceutical Quality by Design

by Tamás Sovány, Katalin Kristó and Ildikó Csóka

Pharmaceutics 2024, 16(6), 832; https://doi.org/10.3390/pharmaceutics16060832 - 19 Jun 2024

Viewed by 681

Abstract

The introduction of the Quality by Design concept in 2004 has brought a paradigm shift in the pharmaceutical industry as well as a new era in pharmaceutical research and development [...] Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

Research

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15 pages, 3027 KiB

Open AccessArticle

Methods for Developing a Process Design Space Using Retrospective Data

by Miquel Romero-Obon, Pilar Pérez-Lozano, Khadija Rouaz-El-Hajoui, Marc Suñé-Pou, Anna Nardi-Ricart, Josep M. Suñé-Negre and Encarna García-Montoya

Pharmaceutics 2023, 15(11), 2629; https://doi.org/10.3390/pharmaceutics15112629 - 16 Nov 2023

Viewed by 1555

Abstract

Prospectively planned designs of experiments (DoEs) offer a valuable approach to preventing collinearity issues that can result in statistical confusion, leading to misinterpretation and reducing the predictability of statistical models. However, it is also possible to develop models using historical data, provided that [...] Read more.

Prospectively planned designs of experiments (DoEs) offer a valuable approach to preventing collinearity issues that can result in statistical confusion, leading to misinterpretation and reducing the predictability of statistical models. However, it is also possible to develop models using historical data, provided that certain guidelines are followed to enhance and ensure proper statistical modeling. This article presents a methodology for constructing a design space using process data, while avoiding the common pitfalls associated with retrospective data analysis. For this study, data from a real wet granulation process were collected to pragmatically illustrate all the concepts and methods developed in this article. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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13 pages, 1603 KiB

Open AccessArticle

Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica

by Majed Alrobaian, Ahmed Alalaiwe, Ziyad S. Almalki and Mohamed H. Fayed

Pharmaceutics 2023, 15(11), 2552; https://doi.org/10.3390/pharmaceutics15112552 - 29 Oct 2023

Viewed by 1362

Abstract

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin [...] Read more.

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin (CNG), facilitating high-speed DC tableting. This was accomplished through a single-step dry coating process using hydrophilic nano-sized colloidal silica. A 3² full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X₁) and mixing time (X₂). Flow, bulk density, and compaction properties of CNG–silica blends were investigated, and the optimized blend was subsequently compressed into tablets using the DC technique. A regression analysis exhibited a significant (p ≤ 0.05) influence of both X₁ and X₂ on the characteristics of CNG with a predominant effect of X₁. Additionally, robust tablets were produced from the processed powders in comparison with those from the control batch. Furthermore, the produced tablets showed significantly lower tablet ejection forces than those from the control batch, highlighting the lubrication impact of the silica nanoparticles. Interestingly, these tablets displayed improved disintegration time and dissolution rates. In conclusion, a dry coating process using silica nanoparticles presents a chance to address the poor flow and tableting problems of CNG, while minimizing the need for excessive excipients, which is crucial for the effective development of a small-sized tablet and the achievement of a cost-effective manufacturing process. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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24 pages, 15096 KiB

Open AccessArticle

Quality by Design-Guided Systematic Development and Optimization of Mucoadhesive Buccal Films

by Alharith A. A. Hassan, Katalin Kristó, Yousif H.-E. Y. Ibrahim, Géza Regdon, Jr. and Tamás Sovány

Pharmaceutics 2023, 15(10), 2375; https://doi.org/10.3390/pharmaceutics15102375 - 23 Sep 2023

Viewed by 1801

Abstract

Mucoadhesive buccal films have found increased popularity in pharmaceutical drug delivery due to the several advantages that they possess. The present study strives to develop and optimize chitosan-based mucoadhesive buccal films by relying on quality-by-design (QbD) principles. Previous knowledge and experience were employed [...] Read more.

Mucoadhesive buccal films have found increased popularity in pharmaceutical drug delivery due to the several advantages that they possess. The present study strives to develop and optimize chitosan-based mucoadhesive buccal films by relying on quality-by-design (QbD) principles. Previous knowledge and experience were employed to firstly identify the critical quality attributes (CQAs), followed by a thorough risk assessment, which led to the selection of seven critical material attributes and process parameters, namely, the polymer grade and concentration, the plasticizer type and concentration, the citric acid (CA) concentration, the amount of the casted solution, and the drying condition. Their effects on the breaking hardness and mucoadhesivity, selected as CQAs, were investigated in three steps by three designs of the experiment (DoE). The medium molecular weight of chitosan (CH) was the preferred choice in the optimized formulation, and its concentration was the most important factor affecting the CQAs, thickness, and moisture content of the films. It was found that 0.364 g/cm² was the suitable amount of the casting solution, and its optimum drying conditions were presented in the form of a design space. Glycerol (Gly) was the best choice as a plasticizer, and a design space representing several combinations of CH and CA concentrations that produce films with the required quality was constructed at a fixed concentration of 35% Gly. A formula from this design space was selected and employed to load with two model drugs to test its drug-carrying properties for drugs with different physicochemical characteristics. Uniform drug distribution with an immediate release profile was achieved in both drugs, although one of the CQAs was outside of the specifications in the case of lidocaine-containing film. To summarize, the obtention of the optimum mucoadhesive buccal film based on CH was efficiently facilitated by the rational application of QbD principles and the DoE approach. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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16 pages, 1872 KiB

Open AccessEditor’s ChoiceArticle

Application of Quality by Design Principles to the Development of Oral Lyophilizates Containing Olanzapine

by Maja Bjelošević Žiberna and Pegi Ahlin Grabnar

Pharmaceutics 2023, 15(7), 1967; https://doi.org/10.3390/pharmaceutics15071967 - 17 Jul 2023

Viewed by 1315

Abstract

Oral lyophilizates are intended for application to the oral cavity or for dispersing in water. The purposes of this research were: (i) to set up the quality by design approach in the development of oral lyophilizates for drug incorporation; and (ii) to evaluate [...] Read more.

Oral lyophilizates are intended for application to the oral cavity or for dispersing in water. The purposes of this research were: (i) to set up the quality by design approach in the development of oral lyophilizates for drug incorporation; and (ii) to evaluate the established approach by comparing its outcomes with experimentally obtained results. Within the knowledge space, properties about drugs, excipients, and the lyophilization process were acquired, followed by the determination of critical quality attributes via risk identification. Risks were assessed by failure mode and effective analysis, which recognized critical material attributes, i.e., type, concentration, particle size, solubility of drug and excipients, while as main critical process parameters, cooling rate, shelf temperature, and chamber pressure during drying were pointed out. Additionally, design space was established using the Minitab^® 17 software and valued with an 88.69% coefficient of determination. A detailed comparison between the model and experimental results revealed that the proposed optimal compositions match in the total concentration of excipients (6%, w/w) in the pre-lyophilized liquid formulation, among which mannitol predominates. On the other hand, a discrepancy regarding the presence of gelatin was detected. The conclusion was that the set model represents a suitable onset toward optimization of drug-based oral lyophilizates development, preventing unnecessary investment of time and resources. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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28 pages, 4013 KiB

Open AccessArticle

Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme

by Merima Šahinović, Alharith Hassan, Katalin Kristó, Géza Regdon, Jr., Edina Vranić and Tamás Sovány

Pharmaceutics 2023, 15(3), 995; https://doi.org/10.3390/pharmaceutics15030995 - 20 Mar 2023

Cited by 4 | Viewed by 3738

Abstract

For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive [...] Read more.

For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept. LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: −4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (−0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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16 pages, 2345 KiB

Open AccessArticle

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology

by Ahmed Alalaiwe, Mohammad A. Alsenaidy, Ziyad S. Almalki and Mohamed H. Fayed

Pharmaceutics 2023, 15(3), 923; https://doi.org/10.3390/pharmaceutics15030923 - 12 Mar 2023

Cited by 4 | Viewed by 2043

Abstract

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form [...] Read more.

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (3²) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10–40% w/w) and partially pre-gelatinized starch (PPGS; 2–10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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12 pages, 2215 KiB

Open AccessArticle

Feasibility of Child-Resistant and Senior-Friendly Press-Through Packages: Potential of Different Materials

by Kiyomi Sadamoto, Hiroyuki Ura, Mikio Murata, Masaho Hayashi and Kiyoshi Kubota

Pharmaceutics 2023, 15(3), 890; https://doi.org/10.3390/pharmaceutics15030890 - 9 Mar 2023

Cited by 1 | Viewed by 1857

Abstract

Press-through packaging (PTP) is the most common type of drug packaging in Japan, and a production procedure for PTP has been established at an acceptable cost. However, unknown problems and new needs with regard to safety among users of various age-groups still need [...] Read more.

Press-through packaging (PTP) is the most common type of drug packaging in Japan, and a production procedure for PTP has been established at an acceptable cost. However, unknown problems and new needs with regard to safety among users of various age-groups still need to be examined. Considering accident reports involving children and older adults, the safety and quality of PTP and new forms of PTP, such as child-resistant and senior-friendly (CRSF) packaging, should be evaluated. We conducted an ergonomic study on children and older adults to compare types of commonly used PTP and new varieties of PTP. Opening tests were attempted by children and older adults using a common type of PTP (Type A) and child-resistant (CR) PTP (Types B1 and B2) made from soft aluminum foil. The same opening test was conducted on older patients with rheumatoid arthritis (RA). The results showed that CR PTP was difficult for children to open: only 1 out of 18 children could open Type B1. On the other hand, all eight of the older adults could open Type B1, and eight patients with RA could easily open Types B1 and B2. These findings suggest that the quality of CRSF PTP can be improved with the use of new materials. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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29 pages, 4259 KiB

Open AccessArticle

Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product

by Jonas Pielenhofer, Sophie Luise Meiser, Karsten Gogoll, Anna-Maria Ciciliani, Mark Denny, Michael Klak, Berenice M. Lang, Petra Staubach, Stephan Grabbe, Hansjörg Schild, Markus P. Radsak, Hilde Spahn-Langguth and Peter Langguth

Pharmaceutics 2023, 15(2), 514; https://doi.org/10.3390/pharmaceutics15020514 - 3 Feb 2023

Cited by 7 | Viewed by 3418

Abstract

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment [...] Read more.

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process’s milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300–400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 “IMI-Gel” batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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17 pages, 9209 KiB

Open AccessArticle

Influence of Roll Speed during Roll Compaction and Its Effect on the Prediction of Ribbon Solid Fraction

by Martin Lück, Matthias De Saeger and Peter Kleinebudde

Pharmaceutics 2022, 14(11), 2399; https://doi.org/10.3390/pharmaceutics14112399 - 7 Nov 2022

Cited by 3 | Viewed by 2549

Abstract

Influence of the roll speed (RS) during roll compaction on ribbon, granule, tablet properties and its effect on the prediction of the ribbon solid fraction at-gap is often neglected or controversially discussed. The aim of this study was to investigate the [...] Read more.

Influence of the roll speed (RS) during roll compaction on ribbon, granule, tablet properties and its effect on the prediction of the ribbon solid fraction at-gap is often neglected or controversially discussed. The aim of this study was to investigate the effect of the RS systematically. Microcrystalline cellulose (MCC) and lactose were compressed at several maximum roll pressures (

P_{m a x}

) and RS combinations using a gap-controlled roll compactor. The ribbon solid fraction after elastic recovery (

S F_{r i b b o n}

), granule size distribution and tabletability of the granules as well as the ribbon solid fraction at-gap

(S F_{g a p})

were measured. The Midoux number (Mi), derived from the Johanson model, was used to predict the ribbon solid fraction at-gap

(S F_{M i}

). The measured

S F_{g a p}

and the predicted

S F_{M i}

lead to a prediction accuracy (PA) of the Midoux number. The results are highly dependent on the material used and the applied

P_{m a x}

. Higher plasticity of the material leads to a reduction in

S F_{r i b b o n}

and granule size with increasing RS. However, this effect can be overcome or reduced by adjusting

P_{m a x}

above the yield pressure of the used material. These results allow for higher roll speeds as a potential upscaling method in roll compaction. On the other side, the PA of the Midoux number was also reduced with increased RS for MCC and had no effect for lactose. Thus, RS seems to be an important factor in the prediction of roll compaction processes and prediction models should include RS as a parameter to improve their accuracy. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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14 pages, 2990 KiB

Open AccessArticle

Design of Experiments as a Tool to Optimize the Process of Coating Minitablets with Commercial Gastro-Resistant Coating Mixtures

by Maja Frankiewicz and Małgorzata Sznitowska

Pharmaceutics 2022, 14(9), 1816; https://doi.org/10.3390/pharmaceutics14091816 - 29 Aug 2022

Cited by 4 | Viewed by 2380

Abstract

According to the Quality by Design (QbD) concept, Design of Experiment (DoE) was used to indicate critical process parameters and optimize the fluid bed coating of minitablets in a laboratory size batch. Full factorial design was employed to increase knowledge of the process [...] Read more.

According to the Quality by Design (QbD) concept, Design of Experiment (DoE) was used to indicate critical process parameters and optimize the fluid bed coating of minitablets in a laboratory size batch. Full factorial design was employed to increase knowledge of the process for three kinds of minitablet (MT) cores using two commercial gastro-resistant coating mixtures. The statistical analysis showed that different critical process parameters were indicated for the tested minitablets: X3: the coating mixture flow rate for MTs with pantoprazole sodium and Eudragit L; X2: the product temperature; X3 and X4: the spraying pressure for MTs with pantoprazole sodium and Acryl Eze II; and X1 and X2: MTs with diclofenac sodium. Such differences were the result of features, such as the sub-coat, size, and mass of the cores and the core and coating mixture composition. No optimal parameters were found for any of the tested MT types. Therefore, DoE should be considered as a statistical tool to individually optimize the process for the product, equipment, and tested parameters. However, optimization of the fluid bed coating allowed us to predict the values of the process parameters necessary to obtain good-quality products. Therefore, fluid bed coating may be successfully used to obtain modified-release MTs of high quality after applying the statistical tool DoE. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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25 pages, 4595 KiB

Open AccessArticle

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives

by Zsófia Németh, Ildikó Csóka, Reza Semnani Jazani, Bence Sipos, Henrik Haspel, Gábor Kozma, Zoltán Kónya and Dorina Gabriella Dobó

Pharmaceutics 2022, 14(9), 1798; https://doi.org/10.3390/pharmaceutics14091798 - 26 Aug 2022

Cited by 69 | Viewed by 4483

Abstract

Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum [...] Read more.

Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 3² fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and −36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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17 pages, 2108 KiB

Open AccessArticle

Design Space Approach for the Optimization of Green Fluidized Bed Granulation Process in the Granulation of a Poorly Water-Soluble Fenofibrate Using Design of Experiment

by Mohamed H. Fayed, Ahmed Alalaiwe, Ziyad S. Almalki and Doaa A. Helal

Pharmaceutics 2022, 14(7), 1471; https://doi.org/10.3390/pharmaceutics14071471 - 15 Jul 2022

Cited by 6 | Viewed by 2121

Abstract

In the pharmaceutical industry, the systematic optimization of process variables using a quality-by-design (QbD) approach is highly precise, economic and ensures product quality. The current research presents the implementation of a design-of-experiment (DoE) driven QbD approach for the optimization of key process variables [...] Read more.

In the pharmaceutical industry, the systematic optimization of process variables using a quality-by-design (QbD) approach is highly precise, economic and ensures product quality. The current research presents the implementation of a design-of-experiment (DoE) driven QbD approach for the optimization of key process variables of the green fluidized bed granulation (GFBG) process. A 3² full-factorial design was performed to explore the effect of water amount (X₁; 1–6% w/w) and spray rate (X₂; 2–8 g/min) as key process variables on critical quality attributes (CQAs) of granules and tablets. Regression analysis have demonstrated that changing the levels of X₁ and X₂ significantly affect (p ≤ 0.05) the CQAs of granules and tablets. Particularly, X₁ was found to have the pronounced effect on the CQAs. The GFBG process was optimized, and a design space (DS) was built using numerical optimization. It was found that X₁ and X₂ at high (5.69% w/w) and low (2 g/min) levels, respectively, demonstrated the optimum operating conditions. By optimizing X₁ and X₂, GFBG could enhance the disintegration and dissolution of tablets containing a poorly water-soluble drug. The prediction error values of dependent responses were less than 5% that confirm validity, robustness and accuracy of the generated DS in optimization of GFBG. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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12 pages, 3490 KiB

Open AccessArticle

Raman Mapping-Based Reverse Engineering Facilitates Development of Sustained-Release Nifedipine Tablet

by Ningyun Sun, Liang Chang, Yi Lu and Wei Wu

Pharmaceutics 2022, 14(5), 1052; https://doi.org/10.3390/pharmaceutics14051052 - 13 May 2022

Cited by 2 | Viewed by 3018

Abstract

The development of generic preparations that are bioequivalent to a reference listed drug (RLD) is faced with challenges because some critical attributes of RLDs are commonly unknown to developers. In order to determine these attributes, Raman mapping-based reverse engineering in this study to [...] Read more.

The development of generic preparations that are bioequivalent to a reference listed drug (RLD) is faced with challenges because some critical attributes of RLDs are commonly unknown to developers. In order to determine these attributes, Raman mapping-based reverse engineering in this study to analyze a model sustained-release tablet of nifedipine. The Raman mapping results indicate that the size and size distribution of nifedipine are critical to its release pattern and bioavailability. The tablets with a particle size of nifedipine comparable to that of a commercial product, Adalat^®-L, showed similar in vitro release profiles to the RLD. Moreover, a pharmacokinetic study in human volunteers proved the bioequivalence of the two preparations. In conclusion, Raman mapping-based reverse engineering has the potential to facilitate the development of generic preparations. Full article

(This article belongs to the Special Issue Aspects and Implementation of Pharmaceutical Quality by Design)

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