Functionality Of Excipients Research Articles

Self-Nano Emulsifying Drug Delivery System: A Potential Solution to the Challenges of Oral Delivery of Poorly Water-Soluble Drugs

Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-Nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. SNEDDS are isotropic mixtures composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce nanoemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract. SNEDDS has garnered attention during recent years as it improves oral bioavailability, reduces drug dose, and increases drug protection from unsuitable environment in the gastrointestinal tract. It can solve the problems related to the dissolution and bioavailability of the Biopharmaceutics Classifcation System Class II and IV drugs. This review shortly describes the ambiguity between nanoemulsions and microemulsions, mechanism of self-emulsifications, composition and function of various excipients of SNEDDS. This review discusses characterization of SNEDDS, advantage of SNEEDS over other emulsion, biopharmaceutical aspects, and limitation as well as future views. The SNEDDS is a potential formulation for drug delivery. Owing to its small particle size, large surface area, high encapsulation efficiency, and high drug loading, the SNEDDS can improve the rate and extent of oral absorption by maximizing drug solubility in the intestinal absorption site. Moreover, because of the lipid-based formulation of SNEDDS, it can stimulate and enhance lymphatic transport of drugs to avoid hepatic first-pass metabolism, and thus improve their bioavailability.

Studies on the Physicochemical Properties of Coprocessed Starch obtained from <i>Ipomoea batatas</i>

Co-processing has been identified as a tool for enhancing the functionality of excipients. The aim of this research was to extract starch from sweet potato, modify the starch by coprocessing with colloidal silicon dioxide and characterize. Sweet potato starch was extracted from the fresh tubers of Ipomoea batatas collected from Custom market, Maiduguri. Coprocessing with colloidal silicon dioxide at varying ratios of 95:5 and 90:10 using the co-fusion method was carried out. The co-processed mixture was dehydrated with ethanol (99 %), spread on a tray to air dry, passed through a 50 mm sieve and the drying was completed in an oven at 40 °C for 2 hours. Pharmacopoeial and physicochemical characteristics of the starches were assessed. The results obtained showed a significant improvement in the physicochemical properties (swelling and moisture sorption capacities) of the co-processed starches when compared with the native sweet potato starch. The modification of sweet potato starch by coprocessing with colloidal silicon dioxide yielded a starch-based excipient that had better physicochemical properties than the native starch. Thus, it has potential for use as a direct compression excipient.

A comprehensive review on pharmaceutical excipients.

The effectiveness of pharmaceutical drugs depends not only on their active components and manufacturing processes, but also on the role played by pharmaceutical excipients. The traditional definition of excipients as inactive and cost-effective substances has evolved significantly. They are now recognized as essential elements of drug formulations, constituting 80-90% of the final product. The rapid advancements in delivery systems, along with scientific, regulatory, financialand technological developments in biopharmaceutics, have generated renewed interest in the use and functionality of excipients, especially in solid dosage forms. This review focuses on the categorization of excipients according to the International Pharmaceutical Excipient Council (IPEC) and the establishment of guidelines for evaluating the safety of a new proposed excipient.

Overview on Functionality Added Co-processed Excipients for Orodispersible Tablets

Orally disintegrating tablets are an emerging trend in novel drug delivery system and have received ever increasing demand during the last few decades. Orally disintegrating tablets ODTs are the dosage form which will disintegrate in mouth within seconds without need of water. This type of property in dosage form can be attained by addition of different varieties of excipients. But the number of fillers/binders/disintegrant which can be used for ODT formulations is limited because these bulk excipients have to fulfill special requirements, such as being soluble in water, pleasant taste, mouth feel, sweetness, and rapid dispersibility. In recent years drug formulation scientists have recognized that single component excipients do not always provide the requisite performance to allow certain active pharmaceutical ingredients to be formulated or manufactured adequately. New combinations of existing excipients are an interesting option for improving excipient functionality now a day. In excipients mannitol is used as diluents but now a day’s modified mannitol is available which give extensive flow, compression and rapid dispersibility to the tablet e.g. like Orocell, Mannogem EZ, and Pearlitol SD 200. The current review article is prepared to have a look over the recent development in excipient technology and the approaches involved in development of such excipients. It emphasizes on the different examples of functionality added materialsalso called as multifunctional co processed excipients available in market such as Ludiflash, Pharmburst, and F- MELT.

DIRECT COMPRESSIBLE AND CO-PROCESSED EXCIPIENTS- A REVIEW

The demands on the functionality of excipients are increasing day by day because of the emergence of high-speed tableting machines and the use of direct compression methods for tableting. Direct compressible is the preferred method for the preparation of tablet. Excipient play an important role in formulating a dosage form. these are the ingredient which along with active pharmaceutical ingredient make up the dosage forms. Excipient act as protective agent, bulking agent and can also be used sources of excipients along with their uses, and these Can be used for different activities. The current review article highlights the information about Direct compressible and co-processing excipients and their advantages. Also, the recent developments in excipient technology with special emphasis on natural combinations that could be used as co-processed excipients are briefly discussed.

Stabilizers and their interaction with formulation components in frozen and freeze-dried protein formulations.

This review aims to provide an overview of the current knowledge on protein stabilization during freezing and freeze-drying in relation to stress conditions commonly encountered during these processes. The traditional as well as refined mechanisms by which excipients may stabilize proteins are presented. These stabilizers encompass a wide variety of compounds including sugars, sugar alcohols, amino acids, surfactants, buffers and polymers. The rational selection of excipients for use in frozen and freeze-dried protein formulations is presented. Lyophilized protein formulations are generally multicomponent systems, providing numerous possibilities of excipient-excipient and protein-excipient interactions. The interplay of different formulation components on the protein stability and excipient functionality in the frozen and freeze-dried systems are reviewed, with discussion of representative examples of such interactions.

Impact of the manufacturing technique on the dissolution-enhancement functionality of PEG4000 in Cilostazol tablets

Cilostazol was selected as poorly-soluble model drug to investigate the impact of the manufacturing method on the excipient functionality of PEG4000 at various levels. Powder blends were prepared by direct compression (DC), wet granulation (WG) and hot-melt extrusion (HME). Characteristics of these blends and their compressed tablets were investigated by standard techniques. Solid-state characterization was carried out using differential scanning calorimetry (DSC). While DC trials were found with no significant differences, WG and HME showed contrasting enhancement and retardation effects regarding the dissolution profile of Cilostazol tablets depending on the level of PEG4000 incorporated. The optimal enhancement of dissolution was obtained at 10% w/w PEG4000 for tablets prepared by HME. DSC analysis indicated that no solid solutions were formed at such low levels of PEG4000during processing by either manufacturing techniques. Consequently, the wetting functionality and dissolution enhancement of PEG4000 was revealed to be level- and manufacturing method dependent.

Just how prevalent are peptide therapeutic products? A critical review.

How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic peptide products and the formulations approved by the United States Food and Drug administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). This review also provides an in-depth analysis of dosage forms and administration routes for delivering peptide therapeutics, including injectables, oral dosage forms, and other routes of administration. We discuss the function of excipients in parenteral formulations in detail, since most peptide therapeutics are parenterally administered. We provide case studies of alternate delivery routes and dosage forms. Based on our analysis, therapeutic peptides administered as injectables remain the most commonly used dosage forms, particularly in the form of subcutaneous, intravenous, or intramuscular injections. In addition, therapeutic peptides are formulated to achieve prolonged release, often through the use of polymer carriers. The limited number of oral therapeutic peptide products and their poor absorption and subsequent low bioavailability indicate a need for new technologies to broaden the formulation design space. Therapeutic peptide products may also be delivered through other administration routes, including intranasal, implant, and sublingual routes. Therefore, an in-depth understanding of how therapeutic peptides are now formulated and administered is essential to improve peptide delivery, improve patient compliance, and reduce the healthcare burden for these crucial therapeutic agents.

Functionality of disintegrants with different mechanisms after roll compaction.

The aim of this study was to investigate the functionality of two disintegrants (crospovidone and croscarmellose sodium) in tablet formulations processed via roll compaction and subsequent tableting. The influence of different fillers and the effect of sodium lauryl sulfate on the disintegration process were studied using full factorial design. For a direct comparison of disintegrant functionality, the center point formulations were manufactured via direct compression. Tablet characteristics, such as tensile strength, solid fraction, disintegration time and mechanism, and dissolution profile were determined. The results allow the conclusion that the functionality of the disintegrants is impaired by dry granulation. Both the disintegration mechanism and the disintegration time were different when comparing tablets made after dry granulation and by direct compression. The effect was more pronounced on the functionality of crospovidone than on that of croscarmellose sodium. In addition, sodium lauryl sulfate showed a notable influence on all tablet properties due to its lubricating effect. The variation of the filler also had a remarkable effect on the tablet characteristics. The results link excipient functionality to drug product properties depending on the applied manufacturing process and could contribute to extend the Manufacturing Classification System to excipient characteristics.

Development of alginate esters as novel multifunctional excipients for direct compression

Methyl ester derivatives of alginic acid have been evaluated as potential multifunctional excipients for pharmaceutical direct compression. The use of alginic acid as an excipient in tablet formulation is limited because of certain drawbacks such as low tablet hardness and poor compressibility. The objective of this work is to improve these properties through esterification of alginic acid, chemical modification commonly used for enhancing the functionality of tableting excipients. It has been observed that the degree of methylation (DM) has a profitable impact in the physico-chemical and mechanical properties of the obtained materials. In general, an increase in the degree of methylation yielded tablets with higher tensile strength and better compressibility. Furthermore, modified alginates exhibited extended disintegration times compared to native alginic acid due to the introduced hydrophobicity. Finally, the functional versatility of the modified alginates as disintegrating and filling/binding agents was tested by formulating them with microcrystalline cellulose and lactose.

A study on the impact of HPMC viscosity grade and proportion on the functional properties of co-freeze-dried mannitol-HPMC cushioning excipients for compacted MUPS

The co-processing of multiple excipients is driven by the potential of diversifying the properties and functionality of excipients when they are combined. Bulk freeze-drying-milling is a novel secondary processing approach to develop co-processed excipients. It offers a significant advantage of formulation flexibility. This study was designed to systematically investigate the impact of 3 factors, hydroxylpropyl methyl cellulose (HPMC) viscosity grade, mannitol to HPMC ratio and particle size fraction on the functional properties of freeze-dried (FD) mannitol-HPMC cushioning excipients produced for multi-unit pellet system tableting. Based on the results, the investigated formulation variables were significant in determining the functional properties of the FD-mannitol-HPMC cushioning excipients. Among the formulations, FD-mannitol-HPMC F4M (3:1 ratio) excipients exhibited the best cushioning performance. It was postulated that the protective effects of the cushioning excipient were brought about by its propensity for rearrangement around the coated pellets to reduce detrimental pellet-pellet contact and ability to absorb damaging compressive forces. Conversely, FD-mannitol-HPMC vLV (3:1 ratio) had cushioning effects but showed short disintegration time while maintaining adequate tablet tensile strength. Overall, the results of this study highlighted the impact of formulation variables on the functional properties of the cushioning excipients, arising from an interplay of the freeze-dried particle properties.

A review: Pharmaceutical excipients of solid dosage forms and characterizations

Excipients play an important role in formulating dosage forms. Exertion is empowered to help manufacture, provide, or collect dosage forms. Although considered pharmacological, excipients may consider a drug, due to chemical or physical interactions with the composition of the drug. Excipients have many functions in pharmaceutical dosage forms, including enhancing active ingredients in dosage forms, assisting active ingredients, disintegration, lubricants, binders, and suppliers. Each excipient has different characteristics. In this review, a library of studios is provided relating to the function, function, and content of solid excipients in a solid sedan. Various choices can be used on different compositions; resulting, this difference is also different. In this example, describe the types of excipients that can be used for various components in solid preparations that can be used in the formulation of solid preparations and select the right type of excipient according to the character of the desired solid preparation. In this review also presented a method, combining in and characterizing solid excipients to see the quality. The most commonly used methods for analysis of solid excipients are flow properties, compressibility index, Hausner index ratios, and angle of repose, while the instrumentation commonly used is Fourier transform infrared spectroscopy (FTIR), H and C-Nucleo magnetic resonance (H-CNMR), Scanning electron microscopy (SEM), Particle size analysis (PSA), X-ray diffraction (XRDP) and Differential scanning calorimeter (DSC).

Decision Support for Excipient Risk Assessment in Pharmaceutical Manufacturing.

Excipients have always been a key input into pharmaceutical products, profoundly affecting product quality. Currently, most of our knowledge of excipient critical quality attributes is empirical, gained through experience, and shared through publications and other sources. The behavior of excipients is complicated, with many different failure modes that depend on the type of dosage form. Even within the same dosage form, there can be multiple failure modes depending on the manufacturing method. This complex behavior creates many possible combinations to assess when designing a formulation or evaluating regulatory submissions. Formulation science could be improved if data from different sources could be made widely available through an interactive system using a consistent, structured format to help formulators and regulators assess the risk of excipient usage for a particular dosage form with a particular manufacturing method. This paper describes a decision support system that was created for assessing excipient risk in different types of formulations and considering different types of manufacturing methods, dosage forms, and excipient functionality. The Excipient Risk Assessment System consists of a database that stores knowledge about factors that affect formulation design and a decision support processor that manages selections for creating formulation scenarios and assigning risk. Formulation and risk assessment data are provided by formulation science experts. This enables the system to assess compatibility among excipients, functionality, dosage forms, and manufacturing methods selected for formulations. The interface guides users through the creation of formulation scenarios and displays customized, interactive risk assessment reports for users to search and explore.

Adsorption behavior of some metal ions on nanoparticles used in pharmaceutical matrices: Application to laboratory made drug formulation

The adsorption behavior of some metal ions (Pb, Mn, Mg, Zn and Ca) was studied on silicon dioxide nanoparticles, SiO2 NP, alone and its mixture with microcrystalline cellulose, MCC, powder (1:1) as drug carriers in pharmaceutical preparations. The effect of different conditions as temperature and pH on adsorption was investigated. It was found that upon increasing the temperature, the ability of the adsorbent material increases. The pH of the metal solution has the same effect as temperature till pH 8. However, above pH 8 the adsorbent material began to lose its adsorption efficiency. Although, the use of SiO2 NP mixture with MCC powder can improve the excipient functionality, it is important to take into consideration their metal adsorption behavior. The study was applied on laboratory made drug formulation contains different drug carriers. The study points at the importance of adjusting the permissible level of metals in different active and inactive ingredients used in pharmaceutical preparations containing nanoparticles as drug carriers. The type of nanoparticles used and the pH of these preparations are important factors affecting the metal adsorption behavior. At the maximum temperature of adsorption, the calculated metal adsorption capacity of a mixture of MCC and SiO2 NP (1:1) compared to SiO2 NP alone was found to be 0.2043 and 0.1169 for Pb, 0.1948 and 0.1041 for Zn, 0.2114 and 0.1207 for Mg, 0.2220 and 0.1222 for Ca and 0.2068 and 0.1054 for Mn, respectively. Flame atomic spectrometry was used for determining metal remained concentration after adsorption.

Co Processed Excipients for Tabletting: Review Article

This main aim of the current review article is to provide a complete overview on recent development in excipient technology and the approaches involved in development of such excipients. Formulation scientists recognized that single component excipients do not always provide the requisite performance to allow certain active pharmaceutical ingredients to be formulated or manufactured adequately and they have focused their attention on the production of multifunctional excipients with enhanced performance to meet the needs of formulation experts in terms of costs of production, enhanced excipient functionality and quality of tablets. Manipulation in the functionality of excipient is provided by the co-processing of two or more existing excipients. Tablet manufacturing has been changed by the introduction of the direct-compression process and high-speed machines. These two developments have increased the demands on the functionality of excipients in terms of flow and compression properties. Direct compression is the preferred method for the preparation of tablets. The shift in tabletting toward direct-compression and high-speed manufacturing has forced the excipient industry to search for new excipients. The excipient industry, which has largely been an extension of the food industry, has taken up the novel use of particle engineering and material sciences to pave the way for a new category of functional excipients called co processed excipients. The coprocessing is the most widely explored method for the preparation of directly compressible adjuvants because it is cost effective and can be prepared in-house based on the functionality required.

Excipients functionality: Importance and compendial status

Traditional understanding of excipients as simple, inert and inactive ingredients of pharmaceutical preparations was changed when it became clear that they may significantly affect quality, safety and efficacy of pharmaceutical preparations. Excipients variability caused by differences in raw materials and production process may affect their performance in the final formulation. In order to manufacture/compound drug of acceptable quality it is necessary to identify those characteristics of excipients that are important for their intended function, assess mechanism and extent of their influence on the intended function, and define the acceptable range of their values. These characteristics are known as functionality-related characteristics of excipients, and the way and the extent by which excipients fulfill their intended function in final formulation is defined as their functionality. Having in mind that functionality depends on the final formulation and manufacturing/compounding process, it cannot be generalized, but it can be defined in context of certain pharmaceutical preparation, obtained by certain compounding/manufacturing process. This paper discusses definition, importance and compendial status of functionality and functionality-related characteristics of excipients, as well as functionality-related characteristics as critical quality attributes, from the perspective of QbD concept of drug development.

Particle Engineering of Excipients for Direct Compression: Understanding the Role of Material Properties.

Tablets represent the preferred and most commonly dispensed pharmaceutical dosage form for administering active pharmaceutical ingredients (APIs). Minimizing the cost of goods and improving manufacturing output efficiency has motivated companies to use direct compression as a preferred method of tablet manufacturing. Excipients dictate the success of direct compression, notably by optimizing powder formulation compactability and flow, thus there has been a surge in creating excipients specifically designed to meet these needs for direct compression. Greater scientific understanding of tablet manufacturing coupled with effective application of the principles of material science and particle engineering has resulted in a number of improved direct compression excipients. Despite this, significant practical disadvantages of direct compression remain relative to granulation, and this is partly due to the limitations of direct compression excipients. For instance, in formulating high-dose APIs, a much higher level of excipient is required relative to wet or dry granulation and so tablets are much bigger. Creating excipients to enable direct compression of high-dose APIs requires the knowledge of the relationship between fundamental material properties and excipient functionalities. In this paper, we review the current understanding of the relationship between fundamental material properties and excipient functionality for direct compression.

Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis

With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg-St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5% showed downward curvature indicating a gradual decrease in surface area over time. Conversely, with TR-FB, even when its concentration was increased, the S(t) profile for APAP had a maximum value. The differences between Mg-St and TR-FB could be explained by the differences in extensibility deriving from their morphology. Next, we evaluated the effect of disintegtant concentration using five disintegrants. When disintegrant was added to ethenzamide tablet formulation, an increase in the dissolution rate and S(t) dependent on disintegrant concentration was observed, according to the type of disintegrant. It was found that the water absorption ability of disintegrants had strong correlations with the parameters of S(t). Taken together, this study demonstrates that analysis of S(t) can directly provide useful information, especially about the functionality of pharmaceutical excipients.

Co-Processing of Excipients: A Review on Excipient Development for Improved tabletting Performance

Tablet manufacturing has been changed by the introduction of the direct-compression process and high-speed machines. These two developments have increased the demands on the functionality of excipients in terms of flow and compression properties. Direct compression is the preferred method for the preparation of tablets. The co-processing is the most widely explored method for the preparation of directly compressible adjuvants because it is cost effective and can be prepared in-house based on the functionality required. This review article is in pursuit of giving detailed information on the sources of new excipients, potential advantages of co-processed excipients, material characteristics required for co-processing, methods of preparing directly compressible adjuvants and various co-processed excipients for direct compression available in the market.

Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets.

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale.