Development Of Pharmaceutical Dosage Forms Research Articles

Analytical Method Development and Validation for Estimation of Lapatinib in Formulation by RP-HPLC with Stability Indicating

Reverse-phase high-performance liquid chromatography (RP-HPLC) approach for Lapatinib in pharmaceutical dosage form development and validation. Reverse phase chromatography is easy, practical, and superior in terms of effectiveness, stability, and repeatability. Lapatinib was chosen to be separated using the C18 column, a 250 x 4.6 mm column with 5.0µm particle packing. As lapatinib was exhibiting good peak morphologies and a large amount of resolution, it was created with a mobile phase of water, methanol, and trifluroacetic acid (30:70:0.1) v/v. The analytes were detected at 262nm using a UV detector while the mobile phase was flowing at 1.1 ml/min. Specificity, linearity, accuracy, precision, robustness, limit of detection, and limit of quantitation were used to develop the method and validate it.The method demonstrated a dynamic linear response at 25-75 µg/ml and was shown to be linear with a correlation coefficient (r2) of above 0.999 and limits of detection and quantitation (LOD and LOQ) of 0.45 and 1.35µg, respectively. Degradation of the sample was used to establish the stability indicating RP-HPLC procedures, which were then compared to standards. The relative standard deviation as a percentage was also less than 2%, demonstrating the suggested method's high level of precision.

Preparation and Physicochemical Characterizations of p-Methoxycinnamic acid – Succinic Acid Cocrystal by Solvent Evaporation Technique

Background: PMCA (p-Methoxycinnamic acid) is an active pharmaceutical ingredient derived from Kaempheria galanga L (known as kencur in Indonesia), which is poorly soluble in water. It can cause problems in the development of pharmaceutical dosage forms. Several methods have been carried out to increase the solubility of PMCA such as complex formation with β-cyclodextrin, or solid dispersion. The cocrystal formation method is a solubility enhancement method that has been developed recently.
 Aim: The aim of the study was the preparation and physicochemical characterization of PMCA co-crystal with succinic acid (SA) as its conformer by solvent evaporation technique.
 Methods: PMCA-SA cocrystal was made by the solvent evaporation method with a 1:1 molar ratio. Physicochemical characterization of PMCA and SA cocrystal was performed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscope (SEM).
 Results: The DSC thermogram showed a decrease in the melting point of cocrystal compared to PMCA (173.55˚C), SA (187.55˚C), and its physical mixture (159.53˚C). The cocrystal thermogram displayed an endothermic peak at 158.46 ° C. Diffractogram of PMCA- SA cocrystal exhibited new diffraction peaks at an angle of 2θ = 21.92; 25.91 and 39.25˚ which was not found in the diffractogram of every single component nor its physical mixture. SEM photomicrograph showed PMCA-SA cocrystal as a rod-shaped crystal that had a different surface morphology and smaller size than the constituent materials.
 Conclusions: Based on the physicochemical characterization data above, it could be ascertained that PMCA-SA cocrystals had formed, these cocrystals were expected to increase the solubility of PMCA in water.

Ibuprofen syrup made by mixed solubilization technique

The aim of the present study was to prepare a liquid dosage form (syrup) of a NSAID (ibuprofen) by mixed solvency technique. The syrup formulation was prepared by using mixed hydrotropic method in which potassium citrate, sodium citrate, potassium acetate and disodium hydrogen phospahte were used as hydrotropes. Glycerine and tween 80 were also used in the formulation. The syrup was prepared by agitation method. At first solubility of the model drug Ibuprofen was identified by dissolving it with different hydrotropes. It was observed that the solubility of ibuprofen increased with increase in concentration of the hydrotropes. However, it is difficult to develop a formulation with very concentration of hydrotropes. Therefore, co-solvent and surfactants were also added to enhance the solubility of the ibuprofen. Glycerine and tween 80 were used along with blends of hydrotropes to increase the solubility of Ibuprofen. The results, showed 3000 times increase in solubility of the ibuprofen drug. Also, the drug content of the prepared formulation was found to be 99.67% which proved the mixed solubilizing technique as a efficient and stable method for development of pharmaceutical dosage forms.

Characterization, solubility and stability of amentoflavone polymorphs

Amentoflavone (AMF) is a biflavonoid existing in several medicinal plants possessing anti-tumor, anti-inflammatory activities. However, few studies concern about the polymorphic behavior of this active pharmaceutical ingredient (API). In this study, two polymorph forms (form I, Ⅱ) and one amorphous form of AMF were prepared and characterized by scanning electron microscopy, differential scanning calorimetry, thermal gravimetric analysis, single crystal X-ray diffraction, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. Form Ⅱ was identified as a water-ethanol solvate. The solubility properties and physical stabilities of three forms were also investigated. Amorphous AMF demonstrated the best solubility and was dissolved faster than form Ⅰ and form Ⅱ during dissolution. At 40 °C/ 75% RH, form I and amorphous AMF were more stable than form Ⅱ. This study would provide valuable supporting for the further pharmaceutical dosage form development of AMF.

Pengaruh Konsentrasi HPMC-Kitosan terhadap Sifat Fisik dan Aktivitas Antioksidan Serum Ekstrak Pegagan (Centella asiatica L. Urban)

The use of pegagan (Centella asiatica L.) is an important spotlight in the development of pharmaceutical dosage forms, especially in the scope of cosmetic preparations. Pegagan (Centella asiatica L.) contains secondary metabolites such as flavonoids, phenolics, saponins, and steroids which are natural antioxidants from a plant. This study aims to be able to apply the benefits of pegagan (Centella asiatica L.) in the manufacture of pharmaceutical preparations in the form of facial serum made in three concentrations of HPMC as a gelling agent, namely 4%, 6%, and 8%. HPMC is a gelling agent that can affect the antioxidant value contained in topical preparations. The method in making face serum preparations of pegagan (Centella asiatica L.) extract utilizing the combination of HPMC with chitosan which both have the property of influencing the antioxidant properties of serum preparations made and measurement of antioxidant activity using the DPPH attenuation method as measure by UV-Vis spectrophotometry. The serum of pegagan (Centella asiatica L.) extract which has the best antioxidant activity is Formula 1 (F1) with an IC50 value of 110 μg/mL. F1, F2, and F3 are categories of IC50 values ​​which are included in the category of having moderate levels of antioxidant activity.

Antimicrobial and Anti-Colorectal Cancer Activities of Some Volatile Oils

Volatile oils are natural compounds that can be adopted in many drug and cosmetic formulations. Many volatile oils can be extracted from natural plants and they have their own special biological activities. Nine volatile oils including pine oil (P), guava leaf oil (G), lime peel oil (L), cinnamon bark oil (C), sage oil (S), tea tree oil (T) rosemary oil (R), clove oil (CL) and jasmine sambac oil (J) were in vitro tested for anti-microbial activities against various microbes and cytotoxicity properties agianst HCT116 and HT29 cell lines. From our result, for antimicrobial activities, the most effective oil against Gram positive such as Staphylococcus aureus are T, R and L. Only P showed the great inhibition on Gram negative bacteria such as Escherichia coli. C, P, L, T and R also exhibited different inhibitory effects on the pathogenic yeasts depending on the candida species. For the antitumoral activity on colorectal cancer cell lines, C showed the most cytotoxicity on both HCT116 and HT29 cells with IC50 value of 7.7 and 74.0 μg/ml, respectively. The second most cytotoxic was guava oil with the IC50 of 101.2 and 97.91 μg/ml on HCT116 and HT29, respectively. These investigated data may be useful as information for oil selection and development of pharmaceutical dosage forms using these natural volatile oils as the ingredients.

Fluid properties of various Eudragit® solutions in different solvent systems for periodontal pocket injection

Eudragit® are polymethacrylate-based polymers used for pharmaceutical dosage form development especially for sustained drug release devices. Their fluid properties have not been investigated when using organic solvents used in an in situ forming gel (ISG) for periodontal drug delivery via injection. This research attempted to prepare ISG solutions by dissolving Eudragit® E, Eudragit® L, Eudragit® S, Eudragit® RL and Eudragit® RS in different solvents such as dimethyl sulfoxide (DMSO), N-methyl pyrrolidone (NMP), 2-pyrroridone (PYR), eutectic mixture (1:1 menthol:camphor) and clove oil. Type of these solvents influenced on Eudragit® solubility, density, viscosity, rheology and injectability. NMP could dissolve all types of Eudragit®. Whereas, eutectic solvent could dissolve only the Eudragit® E. The other solvent could dissolve only some specific types of Eudragit®. The completely dissolved solutions were selected for investigation. Density of all Eudragit®-loaded solutions appeared higher significantly than that of the solvent. Moreover, Eudragit® L in NMP showed the highest density. The obtained solutions mostly exhibited Newtonian flow. By comparison, the viscosity of Eudragit® RS in NMP was less than Eudragit® RL ≪ Eudragit® S < Eudragit® L, respectively. All of them needed the force of injection <50 N indicating acceptable injectability. Therefore, Eudragit®-loaded solution using NMP as the solvent was chosen for drug loading in future research for periodontitis treatment. Because Eudragit® type and solvent markedly influenced their fluid properties, the application for using Eudragit® solution in pharmaceutical dosage forms should be considered.

The Potential of Optimized Liposomes in Enhancement of Cytotoxicity and Apoptosis of Encapsulated Egyptian Propolis on Hep-2 Cell Line.

Purpose: Development of pharmaceutical dosage forms of natural products has gained great interest recently. Propolis is a natural product with various active compounds and multiple pharmacological activities. Its resinous nature and low bioavailability were obstacles in the optimum use of this magnificent natural product. Aim: This study evaluates the effect of using liposomes as a drug delivery system on the enhancement of the cytotoxic effect of propolis on squamous cell carcinoma cell lines (Hep-2) of head and neck. Methods: An optimized liposomal formulation of propolis was prepared using the conventional thin film hydration method 1, 2. The prepared (Hep-2) cell line was treated with different concentrations of propolis and optimized propolis liposomes for 24 h. The effect of both propolis and propolis liposomes on cell line was investigated using MTT assay, cytological examination, and nuclear morphometric analysis. The effect of the drugs on the cell apoptosis was evaluated using Annexin V. Results: The findings revealed that both propolis and propolis liposomes have a cytotoxic effect on Hep-2 cell line through induction of apoptosis. The effect was dose dependent. However, a statistically significant enhancement in propolis-mediated apoptosis on Hep-2 cells was elucidated due to encapsulation within the prepared liposomes. Conclusion: Liposome is a powerful tool for enhancing the cytotoxicity of propolis against Hep-2 cell line.

Hot Melt Extrusion and its Application in 3D Printing of Pharmaceuticals.

Hot Melt Extrusion (HME) is a continuous pharmaceutical manufacturing process that has been extensively investigated for solubility improvement and taste masking of active pharmaceutical ingredients. Recently, it is being explored for its application in 3D printing. 3D printing of pharmaceuticals allows flexibility of dosage form design, customization of dosage form for personalized therapy and the possibility of complex designs with the inclusion of multiple actives in a single unit dosage form. Fused Deposition Modeling (FDM) is a 3D printing technique with a variety of applications in pharmaceutical dosage form development. FDM process requires a polymer filament as the starting material that can be obtained by hot melt extrusion. Recent reports suggest enormous applications of a combination of hot melt extrusion and FDM technology in 3D printing of pharmaceuticals and need to be investigated further. This review in detail describes the HME process, along with its application in 3D printing. The review also summarizes the published reports on the application of HME coupled with 3D printing technology in drug delivery.

COMPATIBILITY SCREENING OF VIDAGLIPTIN WITH IONIC AND NON-IONIC POLYMERIC EXCIPIENTS FOR THE DESIGN OF EXTENDED RELEASE DELIVERY SYSTEM

Studies of drug-polymer compatibility play an important role in the preformulation stage for the development of pharmaceutical dosage forms. The potential physical and chemical interactions between drugs and polymer can affect the chemical nature, stability and bioavailability of the dosage form and as a result in the therapeutic response in the clinical phase. The present study reveals the thermal and spectroscopic study of physical mixtures of Vildagliptin (VDG) and HPMC in combination with cationic polymers chitosan, anionic polymers NaCMC and nonionic polymers PEO for extended release (ER). In the first phase of the study, differential scanning calorimeter (DSC) was used as tool to detect any interaction. In the next phase, a Fourier Transform Infrared Spectroscopy (FT-IR) technique was used to confirm and to investigate the type of the possible interactions between the components. In both cases, the spectroscopic data revealed that the analysed polymeric excipients did not show any affect on the VDG. Results of the present study indicated the suitability of the HPMC K4M hydrophilic matrix polymers in combination with cationic polymers, anionic polymers and non-ionic polymers in the preparation of extended release formulation of VDG.

Evaluation of Gelling Behavior of Natural Gums and their Formulation Prospects

Abstract: Purpose: Gums and polymers can be found abundantly in the nature from various plants, microbial and marine sources. Their physical and functional characteristics can be customized according to its application in product development. The purpose of this study is to determine the potentiality of natural gums obtained from plant based sources in development of gel formulation and its comparison with the commercially used polymers viz. Carbapol 934, Carboxy Methyl Cellulose, Xanthan, Sodium Alginate. Methods: Gel formulations of varying ranges of polymeric concentrations were prepared and evaluated for its pharmaceutical parameters like pH, viscosity, homogeneity, tensile strength and antimicrobial activity. Results: The analysis of the developed gel formulations indicated that formulations developed using Guar gum possess much better gelling behavior i.e. viscosity and muco-adhesiveness then other selected gums and is more closer to its synthetic counterpart like Carbopol 934. Thus natural gum provides a comparatively broader range of characteristics and eco-friendly approach which enhances its applicability in formulation development. This research work rationalizes the importance of natural gums as gelling agents in development of pharmaceutical dosage forms, cosmetic products and nutraceutical formulations. Key words: Eco-friendly, Gelling agents, Gel Formulations, Muco-adhesiveness, Antimicrobial activity.

Preparation and in vitro characterization of rosuvastatin calcium incorporated methyl beta cyclodextrin and Captisol® inclusion complexes

Despite being the most effective hypolipidemic agent, poor physicochemical properties of Rosuvastatin calcium (RCa) remain challenging obstacles in the development of pharmaceutical dosage forms. Inclusion complexes (ICs) of RCa with cyclodextrin (CD) derivatives; methyl-beta-cyclodextrin (M-β-CD) and sulfobutylether-beta-cyclodextrin (SBE-β-CD; Captisol®) were formulated by kneading and freeze-drying (lyophilization) methods. Pysicochemical properties of ICs were evaluated by SEM, DSC, XRD, FT-IR, 1H-NMR analyses. Entrapment efficiency (EE), water solubility, in vitro release analyses were also performed. Safety and efficacy of the ICs were analyzed by cytotoxicity and permeation studies on Caco-2 cell lines. Both CDs indicated AL type phase solubility diagrams showing that [1:1] molar ratio. Apparent stability constants (K1:1) were found to be 60.93 M−1 for M-β-CD and 158.07 M−1 for Captisol®. High EE in the range of 93.50–105.40% was achieved. Molar solubility of RCa was increased 3.7- and 4.1-fold with M-β-CD and Captisol® ICs, respectively. In vitro release analyses have indicated the equivalence of dissolution profiles for M-β-CD and Captisol® based ICs to that of pure RCa (f2 > 50). Cytotoxicity studies on Caco-2 cell lines have revealed the safety of ICs for oral use. Permeability studies demonstrated that selected lyophilized F6 formulation has shown the best permeation rate with Papp value of 3.08 × 10−7 cm·s−1. Considering greater water solubility, lower toxicity, high efficiency of complexation as well as, RCa-like permeability and in vitro release behavior at pH 6.8; Captisol® based lyophilized F6 formulation was selected as the best IC to be used in oral dosage forms of RCa.

A Proof of Concept for 3D Printing of Solid Lipid-Based Formulations of Poorly Water-Soluble Drugs to Control Formulation Dispersion Kinetics.

The use of three-dimensional printing (3DP) in the development of pharmaceutical dosage forms is growing rapidly. However, the research is almost exclusively focussed on polymer-based systems with very little reported on 3D printing of lipid-based formulations. Thus, the aim of the work was to explore the feasibility of 3DP technology to prepare solid lipid-based formulations. Here, 3DP was applied for the preparation of solid self-microemulsifying drug delivery systems (S-SMEDDS) with defined surface area to volume (SA/V) ratios. The S-SMEDDS formulations, comprised of Gelucire® 44/14, Gelucire® 48/16 and Kolliphor® P 188 were loaded with fenofibrate or cinnarizine as model drugs. The formulations were printed into four geometrical shapes - cylindrical, prism, cube and torus, and compared to a control cube manually prepared from bulk formulation. The printing process was not significantly affected by the presence of the model drugs. The as-printed S-SMEDDS formulations were characterised using differential scanning calorimetry and wide-angle X-ray scattering. The kinetics of dispersion depended on the SA/V ratio values. The digestion process was affected by the initial geometry of the dosage form by virtue of the kinetics of dispersion of the dosage forms into the digestion medium. This proof of concept study has demonstrated the potential of 3DP for the development of customised S-SMEDDS formulations without the need for an additional carrier or additive and with optimisation could elaborate a new class of dosage forms based on 3D printed lipids. Graphical abstract Lipid based formulations were 3D printed in various shapes to control the surface are to volume ratio and consequently the kinetics of dispersion.

Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs.

Approximately 40% of new chemical entities (NCEs), including anticancer drugs, have been reported as poorly water-soluble compounds. Anticancer drugs are classified into biologic drugs (monoclonal antibodies) and small molecule drugs (nonbiologic anticancer drugs) based on effectiveness and safety profile. Biologic drugs are administered by intravenous (IV) injection due to their large molecular weight, while small molecule drugs are preferentially administered by gastrointestinal route. Even though IV injection is the fastest route of administration and ensures complete bioavailability, this route of administration causes patient inconvenience to visit a hospital for anticancer treatments. In addition, IV administration can cause several side effects such as severe hypersensitivity, myelosuppression, neutropenia, and neurotoxicity. Oral administration is the preferred route for drug delivery due to several advantages such as low cost, pain avoidance, and safety. The main problem of NCEs is a limited aqueous solubility, resulting in poor absorption and low bioavailability. Therefore, improving oral bioavailability of poorly water-soluble drugs is a great challenge in the development of pharmaceutical dosage forms. Several methods such as solid dispersion, complexation, lipid-based systems, micronization, nanonization, and co-crystals were developed to improve the solubility of hydrophobic drugs. Recently, solid dispersion is one of the most widely used and successful techniques in formulation development. This review mainly discusses classification, methods for preparation of solid dispersions, and use of solid dispersion for improving solubility of poorly soluble anticancer drugs.

Some observations on the liquid crystalline and gel behaviors of aqueous dispersions of a prodrug

BMS-830216 is a diprotic acid prodrug of two pKa values (<2 and 6.8) with high apparent solubility at pH ≥ 7. At ∼ pH 4 solutions of BMS-830216 appear to be surface active, in which their surface tension can be reduced from 72 to 65 dynes when its concentrations is above the critical aggregation concentration (CAC∼0.2 mM). Additionally, at this pH, BMS-830216 tends to form liquid crystalline phases (at ≥ 2 mg/mL) in acetate buffer when using tris salt. Furthermore, after raising the concentration beyond 20 mg/g, formation of gel-like dispersions was noted. These gel-like dispersions exhibited a strong elastic strength, significantly impacting the dissolution behavior of the tris salt. Mechanistically, it is likely that BMS-830216 tris salt in solution first forms a lamellar phase followed by formation of a gel phase at higher concentrations (≥20 mg/mL). As indicated by SAXS, the lamellar phase formed seems to have two d-spacing values (∼5 nm and ∼10 nm (weak), which seems to correspond to two molecules connected tail by tail (5 nm). Further investigation is needed for phase identification, as their properties can affect the physical behavior of BMS-830216 in the development of pharmaceutical dosage forms.

Significance of In-Vitro and In-Vivo Correlation in Drug Delivery System

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

Orodispersible Liquisolid Compacts: A Novel Approach to Enhance Solubility and Bioavailability

Orodispersible liquisolid system is the combination of liquisolid technique and orodispersible system. The poor dissolution rate of water insoluble drug is a major drawback for the development of pharmaceutical dosage forms. The oral absorption of drug is most often controlled by dissolution in the gastrointestinal tract. Liquisolid system has been used to enhance dissolution rate of poorly water-soluble drugs. Orodispersible tablets are given in order to provide fast action by disperse in the mouth, without the need of water and make them compliance for paediatric and geriatric patients and to bypass the liver metabolism.

Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with β-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation.

Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with β-cyclodextrin in a poly(Ɛ-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0 g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24 h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing β-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.

FORMULATION AND BIO-AVAILABILITY PARAMETERS OF PHARMACEUTICAL SUSPENSION

The suspension is a biphasic liquid or semi-solid dosage form where the finely divided insoluble solid drug particles are homogeneously dispersed in a liquid or semi-solid medium. The solid drug particles act here as the dispersed phase and the liquid or the semi-solid as the dispersion medium. Suspensions contribute to pharmaceutical dosage form development by supplying drugs that are insoluble in all acceptable medium and often distasteful. Suspension translates such drugs into more bio-available form when compared to capsules, tablets, coated tablets, enteric coated tablets and sustained release products. The dosage form is palatable to the patient and many are doing well when applied to the skin or mucous membrane. This particular dosage form is also applied for injecting drugs into the systemic circulation. Therefore, pharmaceutical suspension finds its application through three different routes of administration namely oral, externally applied suspension and injectable one. The success of any dosage form largely depends on formulation parameters and the factors that influence the bioavailability which ultimately dictate the therapeutic success of the formulated dosage form. Hence, it is obvious to discuss the formulation parameters and the factors influencing bioavailability of suspension for the therapeutic success of it.

Quality by design (QbD) for pharmaceutical area

Abstract: Recent changes and limited resources for drug development and manufacturing have rendered the conventional pharmaceutical quality assurance approach insufficient and have given rise to new research in these areas. To address these research efforts, the FDA improved and modernized the rules governing pharmaceutical manufacturing and product quality in 2002, thereby realizing a paradigm change in the current Good Manufacturing Practices (cGMP). The Quality by Design (QbD) approach has entered the pharmaceutical industry within the last 10 years after the approval of the ICH Q8 in 2005. QbD is based on an understanding of the target product’s quality profile (QTPP) and an assessment of its risks during the design and development of pharmaceutical dosage forms. By determining the critical quality attributes of the drug, including its active ingredient, its excipients, and the processes and design spaces used during the R&D phase, multi-way tracking during the life cycle of the drug can be achieved. This tracking can provide numerous advantages, including flexibility in licensing by decreasing the variation and type modifications in applications of the pharmaceutical product, which result from minimizing the possible issues arising after the release of the product. When all these data are observed, it is clear that the new QbD approach benefits the authorities, the drug manufacturers and the patient. Although QbD has certain challenges during its early stages, it is thought that QbD will benefit pharmaceutical manufacturers. Keywords: Quality by design (QbD), target product quality profile, critical quality attributes, design space, risk assessment.