Excipient

"""Excipients are the integral part of pharmaceutical products development to achieve desired product profile(stability and efcacy). This review deals with understanding of the physicochemical properties of excipients used
in parenteral formulation development for solution, suspension and lyophilized drug products. However, in spite of proper excipients selection, judicious use during formulation manufacturing process based on their critical properties is also important to avoid negative effects such as loss of drug solubility, activity and stability. This paper deals with proper selection of excipients in lyophilized drug products which gives high critical temperature, good bulking properties avoiding melt back and collapse with improved dried product appearance. We have also emphasized on appropriate selection of excipients for solution, suspension injectable dosage forms and linking their physiochemical properties with optimum manufacturing method with suitable case studies. This review will highlight various excipient related issues optimizing product performance with documented references and practical approaches based on scientific justification. The reader will gain better understanding of excipients complexity during stability studies and resolving problems with practical approach."

Many emulsifiers are currently employed in a wide area of pharmaceutical as well as cosmetologic applications to
stabilize the oil-water system. These emulsifiers work on the principle of micelle formation and reduction of
interfacial tension between two immiscible components. Thus the applicability of many surface active agents as
primary emulsifier is dependent on its HLB range. In contrast to these agents, Pemulen polymeric emulsifier is
having wider coverage of the stabilization ability due to its unique emulsification mechanism. Pemulen is a
polymeric emulsifier composed of a block copolymer consisting of a poly acrylic acid similar to the Carbopol resins
presently used to make aqueous and solvent gels in art conservation. These are novel oil-in-water (o/w) emulsifiers
which provide numerous benefits to emulsions prepared with them. Thus the oil droplets are protected by the very
high yield polymeric gel environment formed around the oil droplet by Pemulen and held in place. As a result
Pemulen provides a highly stable emulsion. Due to efficient stabilization, it can be used in number of preparations
which are discussed in this review.

Excipients are included in dosage forms to aid manufacture, administration or absorption. Although considered pharmacologically inert, excipients can initiate, propagate or participate in chemical or physical interactions with drug compounds, which may compromise the effectiveness of a medication. Exicipients are not exquisitely pure. Even for the most commonly used excipients, it is necessary to understand the context of their manufacture in order to identify potential active pharmaceutical ingredients interactions with trace components. Chemical interactions can lead to degradation of the active ingredient, thereby reducing the amount available for therapeutic effect. Physical interactions can affect rate of dissolution, uniformity of dose or ease of administration.

A study of the physico-technical properties of a novel co-processed multicomponent Lentinus tuber regium (LTR) based excipient (fizlent) designed to improve flowability and compressibility of LTR was carried out. A wet mass obtained by solvent evaporation of alcoholic dispersions of LTR, sodium bicarbonate, tartaric and citric acids in proportions of 80, 10, 6.5, 3.5 % w/w respectively was granulated, dried at 60º C and classified with 250µm sieve. Densities (bulk, tapped and particle), flow properties (flow rate, angle of repose, Carr's index, Hausner's ratio), swelling index, hydration capacity, differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and pH were determined for the natural, processed LTR and fizlent. Fizlent appeared as a compactable, tasteless, off-white powder without distinct odour. Aqueous dispersion of it has pH of 6.92 ± 0.13. Results show that a new pharmaceutical grade co-processed excipient, fizlent with enhanced flow, compressibility and dilution potential of 70-80% (paracetamol) and ≤ 30% for metronidazole, ascorbic acid and ibuprofen respectively was developed by particle engineering of Lentinus tuber regium, citric acid, tartaric acid and sodium hydrogen carbonate. Fizlent may be a useful filler-binder with potentials as directly compressible powder especially for most low dose drugs and may possibly serve as superdisintegrant.

Excipients are included in dosage forms to aid manufacture, administration or absorption. Although considered pharmacologically inert, excipients can initiate, propagate or participate in chemical or physical interactions with drug compounds, which may compromise the effectiveness of a medication. Exicipients are not exquisitely pure. Even for the most commonly used excipients, it is necessary to understand the context of their manufacture in order to identify potential active pharmaceutical ingredients interactions with trace components. Chemical interactions can lead to degradation of the active ingredient, thereby reducing the amount available for therapeutic effect. Physical interactions can affect rate of dissolution, uniformity of dose or ease of administration.

The aim of the study presented is to formulate and evaluate Acarbose controlled release matrix tablets by means of different grades of polymer Ethocel and different co-excipients with the intention to see their effects on drug release profile during in vitro dissolution studies. Controlled release dosage forms is gaining rapid popularity due to its positive aspect of reduction in dosage frequency and curtailing side effects. Controlled released tablets of Acarbose were prepared by direct compression method, using Ethocel® Standard 7 Premium and Ethocel® Standard 7 FP premium polymer. The effect of co-excipients including hydroxypropyl methylcellulose (HPMC), Carboxymethyl cellulose (CMC) and starch on the drug placing 30% lactose were also examined. In-vitro studies were carried out with the help of phosphate buffer (pH 7.4) as dissolution medium. Drug release mechanism was assessed by applying various kinetic models. Similarly / dissimilarity factor f2/ f1 were applied for determin...

Co-processing of lactose with synthetic amorphous magnesium silicate has been investigated herein in the context of expanding native lactose applications as a direct compressible excipient. The foregoing was carried out using roll compactor. The obtained excipient was characterized using particle size analysis and compression properties (Kawakita equation). This new excipient showed plastic behavior upon compression, good flowability and crushing strength with shorter disintegration time. Compatibility was tested by differential scanning calorimetry (DSC) and FTIR. The interaction between lactose and Mg silicate proved to be of a physical nature. Formulation with this processed excipient on Mebeverine HCl and Losartan Potassium as model drugs indicated its suitability to be used as a single multifunctional excipient. As a result coprocessed lactose with Mg silicate can be used as a single direct compressible excipient for tablet manufacturing.

The exudates from the incised trunk of Terminalia randii has been evaluated as controlled release excipient in comparison with xanthan gum and hydroxypropylmethylcellulose (HPMC) using carvedilol (water insoluble) and theophylline (water soluble) as model drugs. Matrix tablets were prepared by direct compression and the effects of polymer concentration and excipients-spray dried lactose, microcrystalline cellulose and dicalcium phosphate dihydrate on the mechanical (crushing strength (CS) friability (F) and crushing strength-friability ratio (CSFR)) and drug release properties of the matrix tablets were evaluated. The drug release data were fitted into different release kinetics equations to determine the drug release mechanism(s) from the matrix tablets. The results showed that the CS and CSFR increased with increase in polymer concentration while F decreased. The ranking of CS and CSFR was HPMC > terminalia > xanthan while the ranking was reverse for F. The ranking for t 25 (i.e. time for 25% drug release) at a polymer concentration of 60% was xanthan > terminalia = HPMC. The dissolution time, t 25 , of theophylline matrices was significantly lower (p<0.001) than those of carvedilol matrix tablets. Drug release from the matrices was by swelling, diffusion and erosion. The mechanical and drug release properties of the tablets were significantly (p<0.05) dependent on the type and concentration of polymer and excipients used with the release mechanisms varying from Fickian to anomalous. Terminalia gum compared favourably with standard polymers when used in controlled release matrices and could serve as a suitable alternative to the standard polymers in drug delivery.

This study investigates co-processing lactose with synthetic amorphous magnesium silicate with the aim of expanding the use of directly compressible excipients based on native lactose. The co-processing was performed using roller compaction. The co-processed excipient was characterized using particle size anal. and compression properties (Kawakita equation). The co-processed excipient demonstrated plastic behavior upon compression, good flowability and crushing strength and a shorter disintegration time. Compatibility between the different ingredients of the co-processed excipient, as well as, between the co-processed excipient and model drugs was tested using Differential Scanning Calorimetry (DSC) and Fourier Transform IR spectroscopy (FTIR). The interaction between lactose and magnesium silicate proved to be of a phys. nature. Formulating this co-processed excipient with Mebeverine HCl and Losartan Potassium as model drugs, indicated its suitability as a single multi-functional e...

Enalapril maleate (EM) is known to suffer from incompatibilities in the solid state. This study investigates the destabilizing effect of sodium starch glycolate (SSG) on EM. This was done by varying the mixing ratio and moisture content of binary mixtures. Differential scanning calorimetry and microscopy show a loss of crystallinity of EM at the contact surface with SSG. It is shown that this is followed by decomposition of E to diketopiperazine (DKP). These phenomena are modulated by moisture. The environmental pH turned out to be crucial; when the zwitterion is formed at the appropriate pH, ring closure into DKP is promoted.

The exudates from the incised trunk of Terminalia randii has been evaluated as controlled release excipient in comparison with xanthan gum and hydroxypropylmethylcellulose (HPMC) using carvedilol (water insoluble) and theophylline (water soluble) as model drugs. Matrix tablets were prepared by direct compression and the effects of polymer concentration and excipients-spray dried lactose, microcrystalline cellulose and dicalcium phosphate dihydrate on the mechanical (crushing strength (CS) friability (F) and crushing strength-friability ratio (CSFR)) and drug release properties of the matrix tablets were evaluated. The drug release data were fitted into different release kinetics equations to determine the drug release mechanism(s) from the matrix tablets. The results showed that the CS and CSFR increased with increase in polymer concentration while F decreased. The ranking of CS and CSFR was HPMC > terminalia > xanthan while the ranking was reverse for F. The ranking for t 25 (i.e. time for 25% drug release) at a polymer concentration of 60% was xanthan > terminalia = HPMC. The dissolution time, t 25 , of theophylline matrices was significantly lower (p<0.001) than those of carvedilol matrix tablets. Drug release from the matrices was by swelling, diffusion and erosion. The mechanical and drug release properties of the tablets were significantly (p<0.05) dependent on the type and concentration of polymer and excipients used with the release mechanisms varying from Fickian to anomalous. Terminalia gum compared favourably with standard polymers when used in controlled release matrices and could serve as a suitable alternative to the standard polymers in drug delivery.

A comprehensive approach to target exact
molecular weights and chemical compositions for multimonomeric
statistical copolymers using a new controlled
statistics method with reversible addition−fragmentation chain
transfer free-radical (RAFT) polymerization is presented. The
system chosen to illustrate this procedure is an acrylic
quarterpolymer consisting of methyl acrylate, 2-carboxyethyl
acrylate, 2-hydroxypropyl acrylate, and 2-propylacetyl acrylate,
modeling a well-known macromolecule utilized to deliver
poorly water-soluble drugs (hydroxypropyl methylcellulose
acetate succinate, HPMCAS). The relative reactivities at 70 °C between monomer pairs were measured and employed to predict
the feed ratio necessary for synthesizing well-defined compositions based on the Walling-Briggs model. Application of Skeist’s
equations addressed compositional drift and anticipated the general monomer incorporation distribution as a function of
conversion, which was verified experimentally. This new and simple paradigm combining both predictive models provides
complementary synthetic and predictive tools for designing macromolecular chemical architectures with hierarchical control over spatially dependent structure−property relationships for complex applications such as oral drug delivery.

This study investigates co-processing lactose with synthetic amorphous magnesium silicate with the aim of expanding the use of directly compressible excipients based on native lactose. The co-processing was performed using roller compaction. The co-processed excipient was characterized using particle size analysis and compression properties (Kawakita equation). The co-processed excipient demonstrated plastic behavior upon compression, good flowability and crushing strength and a shorter disintegration time. Compatibility between the different ingredients of the co-processed excipient, as well as, between the co-processed excipient and model drugs was tested using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The interaction between lactose and magnesium silicate proved to be of a physical nature. Formulating this co-processed excipient with Mebeverine HCl and Losartan Potassium as model drugs, indicated its suitability as a single multi-functional excipient. Co-processed lactose with magnesium silicate could be used as a single direct compression excipient for tablet manufacturing.

Bone is in a constant state of remodeling, a lifelong maintenance program of resorption of old bone followed by formation of new bone. The process is regulated by an intricate network of cytokines and hormones. Osteoprotegerin (OPG), the receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) comprise a system of proteins that play a key role in regulating bone remodeling and are well known as targets for developing therapeutics to treat osteoporosis. Recent studies suggest that OPG may also play a role in preventing apoptosis of osteoclasts by the sequestration of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potential negative side effect of therapeutic treatment with OPG. Here we report baculovirus expression and purification of full-length native human OPG and the use of self-interaction chromatography (SIC) to identify excipients that increase the solubility and stability of OPG in aqueous solutions.