Eudragit EPO Research Articles

Role of polymers as crystal growth inhibitors in coprecipitation via solution-enhanced dispersion by supercritical fluids (SEDS) to improve andrographolide dissolution from standardized Andrographis paniculata extract

The poor aqueous solubility and dissolution rate of andrographolide in aqueous gastrointestinal fluids often cause low oral bioavailability. In this work, Andrographis paniculata extract containing 16% andrographolide was coprecipitated with Pluronic F127, Eudragit EPO, and Eudragit L100-55 via solution-enhanced dispersion by supercritical fluids (SEDS) to improve andrographolide dissolution in simulated intestinal fluid (pH 7.4). The SEDS working parameters were set constant as follows: 150 bar, 40 °C, CO2 flow rate 15 L/min (1 bar, 25 °C), liquid feed flow rate 0.5 mL/min, and 25 mg/mL of A. paniculata extract. SEDS coprecipitates formulated with lower Eudragit L100-55:A. paniculata mass ratios exhibited improved andrographolide dissolution in SIF (pH 7.4), while SEDS coprecipitates formulated with either Pluronic F127:A. paniculata or Eudragit EPO:A. paniculata at any mass ratio exhibited poorer andrographolide dissolution (<0.03 mg/mL released in 90 min) than SEDS-precipitated A. paniculata extract powder (0.06 mg/mL released in 90 min). In particular, SEDS coprecipitates formulated with a Eudragit L100-55:A. paniculata mass ratio of 6:25 were found to have the highest andrographolide release and dissolution rate in SIF (pH 7.4) (0.09 mg/mL released in 30 min). SEDS coprecipitation was successful, as indicated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier-transform infrared (FTIR) analysis.

Formulation Development and Evaluation of Oral Sustained Release Suspension containing Antidiarrheal Drug

The research scheme aim at formulation development and evaluation of oral sustained release suspension containing antidiarrheal drug, combination of racecadotril and ofloxacin and the objective to incorporate the fix dose combination of drug in the sustained release to check the suitability of product. To reduce the dosing, frequency and improve the patient compliance particularly in pediatric class to minimize the toxicity due to overdose which often in conventional dosage form. Chewable tablet are not ideal with pediatric and geriatric patient due to need of chewing sustained release suspension will certainly helpful for this patient anti - diarrheal treatment ideally should be effective in combination. The step - by-step studies were performed to develop a stable and acceptable formulation of sustained release oral suspension. Ofloxacin, resin- indion 254, racecadotril, polymer Eudragit EPO were studied for compatibility and interaction study, carried out by FTIR and DSC. Drug, polymer and resin was found to be compatible to each other, therefore selected for further study. Two complexes of each drug were prepared with different objectives and materials. Ofloxacin-Indion complex was prepared for the sustain release action and by batch process in different ratios as 1:1, 1:2, 1:3. Prepared complexes were evaluated for pH and % drug content. Highest drug content of 88.45% was found in 1:3 complex and hence selected for further studies. Rcecadotril-Eudragit EPO polymer complex was prepared for immediate action by kneading method in ratio of 1:1, 1:2, 1:3, were also evaluated for pH and drug content. In case of 1:3 complex 98.45% drug content was found and hence it was chosen for further studies. Sensory in vivo taste was performed to detect the bitterness conc. of drug and complex. The in vivo taste was supported with in vitro drug release study. The result of both studies indicate the satisfactory masking of bitter taste of racecadotril.

Site-specific delivery of polymeric encapsulated microorganisms: a patent evaluation of US20170165201A1

ABSTRACTIntroduction: Probiotics inculde live microorganisms therapeutically effective in the treatment of wide range of diseases. Probiotics possibly stimulates the growth of preferred microorganisms, crowds out potentially harmful microorganisms, and reinforces the body’s natural defense mechanisms. Microencapsulation of probiotic microorganisms protects them from the destructive environment and prolongs their survival. Use of mucoadhesive and pH responsive polymers could impart extended retention, pH sensitive release and mucoadhesive properties to the system. The probiotic formulations could be used for therapeutic, diagnostic, and prophylactic purposes.Areas covered: Layer-by-layer techology was developed for encapsulating Bacillus coagulans employing chitosan and alginate as mucoadhesive polymers (for attachment to the gastrointestinal mucosa) and Eudragit EPO and Eudragit L100 as pH responsive polymers (for site-specific delivery). The formulation was evaluated for layer stability, mucoadhesion capability, protection of microorganisms from biological insults, pH responsive layer removal, in vitro evaluation in three-dimensional intestinal tissue model, probiotic bacterial delivery.Expert opinion: In this patent, a unique layer-by-layer assembly of two differently charged polymers (mucoadhesive and pH repsonsive) was achieved for encapsulating the probiotic microorganism. For assessing the clinical applicability of the invention, further studies may be needed since the conclusions are drawn solely based on in vitro data.

On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing

A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole). The impact of printing modes: simultaneous shell printing and filling (single-phase) or sequential 3D printing of shell bottom, filling and shell cap (multi-phase), nozzle size, syringe volume, and shell structure has been reported. The use of shell thickness of 1.6 mm, and concentric architecture allowed successful containment of liquid core whilst maintaining the release properties of the 3D printed liquid capsule. The linear relationship between the theoretical and the actual volumes from the dispenser reflected its potential for accurate dosing (R2 = 0.9985). Modifying the shell thickness of Eudragit RL capsule allowed a controlled extended drug release without the need for formulation change. Owing to its low cost and versatility, this approach can be adapted to wide spectrum of liquid formulations such as small and large molecule solutions and obviate the need for compatibility with the high temperature of FDM 3D printing process. In a clinical setting, health care staff will be able to instantly manufacture in small volumes liquid capsules with individualised dose contents and release pattern in response to specific patient's needs.

Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release in vivo

Recent work demonstrated remarkable solubilization effects of methacrylate-copolymer Eudragit EPO (EPO) not only with acidic drugs but interestingly also with poorly soluble basic compounds. The current work studied EPO-mediated solubilization effects first in vitro using felodipine (FLP) and tamoxifen (TMX) as model compounds. EPO-containing solutions were subsequently compared in a rat pharmacokinetic study against reference solutions and suspensions. Surprisingly, solution formulations with EPO did not result in an increased relative oral bioavailability. Exposure was reduced for both drugs and plasma-profiles of the EPO solutions showed a delayed and lower maximum plasma concentration compared to the reference formulations. This sustained in vivo release was likely due to combined effects of strong drug-polymer interactions and pH-dependent precipitation of the polymer in the rat intestine. Remarkable was that in vitro drug-polymer coprecipitates did not reveal crystalline drug by polarized light microscopy. Thus, such a formulation approach provides a rather simple opportunity to modify drug release in vivo. However, this may be rather an approach for preclinical formulations, if high peak-to-trough ratios of plasma levels are problematic regarding adverse effects related to Cmax or if plasma concentrations drop too fast below required pharmacological concentrations.

Unexpected Solubility Enhancement of Drug Bases in the Presence of a Dimethylaminoethyl Methacrylate Copolymer.

The methacrylate copolymer Eudragit EPO (EPO) has previously shown to greatly enhance solubilization of acidic drugs via ionic interactions and by multiple hydrophobic contacts with polymeric side chains. The latter type of interaction could also play a role for solubilization of other compounds than acids. The aim of this study was therefore to investigate the solubility of six poorly soluble bases in presence and absence of EPO by quantitative ultrapressure liquid chromatography with concomitant X-ray powder diffraction analysis of the solid state. For a better mechanistic understanding, spectra and diffusion data were obtained by 1H nuclear magnetic resonance (NMR) spectroscopy. Unexpected high solubility enhancement (up to 360-fold) was evidenced in the presence of EPO despite the fact that bases and polymer were both carrying positive charges. This exceptional and unexpected solubilization was not due to a change in the crystalline solid state. NMR spectra and measured diffusion coefficients indicated both strong drug-polymer interactions in the bulk solution, and diffusion data suggested conformational changes of the polymer in solution. Such conformational changes may have increased the accessibility and extent of hydrophobic contacts thereby leading to increased overall molecular interactions. These initially surprising solubilization results demonstrate that excipient selection should not be based solely on simple considerations of, for example, opposite charges of drug and excipient, but it requires a more refined molecular view. Different solution NMR techniques are especially promising tools to gain such mechanistic insights.

Characterizing the pH-Dependent Release Kinetics of Food-Grade Spray Drying Encapsulated Iron Microcapsules for Food Fortification

Iron deficiency is the primary cause of many widespread nutritional diseases including anemia, pregnancy complications, and infant mortality. Release kinetics of iron premixes to be mixed with food items like salt, rice, and tea is a key research objective of many globally active iron fortification efforts. Iron release kinetics of microcapsules of two reverse-enteric coating materials (chitosan and Eudragit EPO) encapsulating various amounts of ferrous sulfate (10–40% of total other solids) were done at three pH values (1, 4, 7) for 2 hours. Chitosan and Eudragit microcapsules contained 2.8–5.3% (w/w) and 1.7–9.6% (w/w) iron, respectively, depicting higher iron loading capacity of Eudragit microcapsules. More than 90% iron was released from most samples within 30 min under stomach conditions (pH 1) and less than 15% iron was released in 2 h under ambient conditions (pH 7), showing suitability of both chitosan and Eudragit EPO as reverse-enteric coatings for iron encapsulation. In terms of reverse-enteric behavior (RE), Eudragit EPO (RE = 2.4) was found to be slightly better than chitosan, suggesting the use of fillers in future research. Higuchi model and Hixson-Crowell model were found to best fit the data, suggesting a transport phenomenon governed by both (a) the diffusion process through the coating material and (b) the dissolution phenomenon resulting in decrease in size of the capsules. Results from this study shall provide guidance for technology development aspects of various food fortification initiatives and an understanding of the iron release from these fortificants during the food preparation and digestion stages.

Impact of Eudragit EPO and hydroxypropyl methylcellulose on drug release rate, supersaturation, precipitation outcome and redissolution rate of indomethacin amorphous solid dispersions

The purpose of this work was to evaluate the impact of polymer(s) on the dissolution rate, supersaturation and precipitation of indomethacin amorphous solid dispersions (ASD), and to understand the link between precipitate characteristics and redissolution kinetics. The crystalline and amorphous solubilities of indomethacin were determined in the absence and presence of hydroxypropylmethyl cellulose (HPMC) and/or Eudragit ® EPO to establish relevant phase boundaries. At acidic pH, HPMC could maintain supersaturation of the drug by effectively inhibiting solution crystallization while EPO increased both the crystalline and amorphous solubility of the drug, but did not inhibit crystallization. The HPMC dispersion dissolved relatively slowly without undergoing crystallization while the supersaturation generated by rapid dissolution of the EPO ASD was short-lived due to crystallization. The crystals thus generated underwent rapid redissolution upon pH increase, dissolving faster than the reference crystalline material, and at a comparable rate to the amorphous HPMC dispersion. A ternary dispersion containing both EPO and HPMC dissolved rapidly, generating an apparent drug concentration that exceeded the amorphous solubility of indomethacin, leading to the formation of a new nanosized droplet phase. These nanodroplets dissolved virtually immediately when the pH was increased. In conclusion, the concentration-time profiles achieved from indomethacin ASD dissolution are a complex interplay of drug release rate, precipitation kinetics and outcome, and precipitate redissolution rate, whereby each of these processes is highly dependent on the polymer(s) employed in the formulation.

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid.

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.

Viewing Molecular and Interface Interactions of Curcumin Amorphous Solid Dispersions for Comprehending Dissolution Mechanisms.

Tautomeric curcumin amorphous solid dispersions (Cur ASDs) formulated with various typical polymers (polyethylene glycol 6000 (PEG), polyvinylpyrrolidone K30 (PVP), Eudragit EPO (EuD), EuD/hydroxypropylmethyl cellulose E50 (HPMC), and PVP/EuD) were probed using in situ Raman imaging plus spectroscopy and molecular modeling techniques, and dissolution mechanism of Cur ASDs were revealed mainly through molecular and interfacial interactions formed between Cur and polymer. The results demonstrated that Cur of keto form existed in Cur-PEG, Cur of enol form was shown in Cur-PVP, while Cur-EuD or Cur ASDs formulated with EuD as component had Cur of keto form and enol form. Hydrogen bond interactions were formed between OH group (PEG, HPMC) with C═O (Cur), and C═O (PVP or EuD) with the OH group (Cur). For Cur ASDs formulated with single polymer, the existed form of Cur was possibly related with the molecular interactions formed between drug and polymer. The wetting effect of excipient and Cur ASDs as well as their fitting equations of contact angle profiles should be seriously considered when analyzing the dissolution mechanism of Cur ASDs. Furthermore, dissolution of Cur-EuD with erosion dissolution pattern was higher than Cur-PVP with diffusion mechanism, and their crystallization pathway can ascribe to solution pathway and solid matrix pathway, respectively. Last but not least, turbidimetry method was effective in determining which excipient was superior and evaluating the function of polymers, including their abilities to improve amorphous Cur loading, drug dissolution, and supersaturation levels. Therefore, both the probing of tautomeric Cur in ASDs at intermolecular level and elucidation of its dissolution mechanism has tremendous value.

FORMULATION AND EVALUATION OF MICROSPHERE BASED ORO DISPERSIBLE TABLETS OF SUMATRIPTAN SUCCINATE

Sumatriptan succinate (SS) is a drug used in the treatment of migraine headaches, but suffers from low patient compliance due to its unpalatable bitter taste. The purpose of the present work was to prepare taste-masked oro dispersible tablets (ODTs) of SS by incorporating drug loaded microspheres into tablets for use in patients experiencing difficulty in swallowing. Microspheres loaded with SS were prepared by solvent evaporation technique. Eudragit EPO, a pH-sensitive aminoalkylmethacrylate copolymer, was used for coating the drug particles, acetone as solvent for the polymer and light liquid paraffin as an encapsulating medium. Drug : polymer ratio of 1:1 was considered to be optimized formulation with a yield of 99.96%, entrapment efficiency of 61.55%, particle size ranging from 30.32 – 90.96μm and in vitro drug release of 85.06% within an hour. FTIR studies suggested absence of drug-excipient interaction. Tablets prepared by direct compression containing microspheres and effervescent agents were evaluated for pre-compression and post-compression parameters. The wetting time, in vitro dispersion time and in vitro disintegration time of the tablets were found to be 39 sec, 35 sec and 32 sec, respectively. The drug release from the tablet was about 85.44% within an hour. The SEM of final ODTs revealed that the microspheres remained intact even after compression. Stability studies indicated that the selected formulation was stable. The results obtained suggested that effective taste-masking was achieved for SS using the technique of microencapsulation and ODTs of acceptable characteristics were obtained by adding effervescent agents followed by direct compression.

A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement.

The methacrylate-copolymer Eudragit EPO (EPO) has raised interest in solubility enhancement of anionic drugs. Effects on aqueous drug solubility at rather low polymer concentrations are barely known despite their importance upon dissolution and dilution of oral dosage forms. We provide evidence for substantial enhancement (factor 4-230) of aqueous solubility of poorly water-soluble anionic drugs induced by low (0.1-5% (w/w)) concentration of EPO for a panel of seven acidic crystalline drugs. Diffusion data (determined by 1H nuclear magnetic resonance spectroscopy) indicate that the solubility increasing effect monitored by quantitative ultraperformance liquid chromatography was caused primarily by molecular API polymer interactions in the bulk liquid phase. Residual solid API remained unaltered as tested by X-ray powder diffraction. The solubility enhancement (SE) revealed a significant rank correlation (rSpearman = -0.83) with rDiffAPI, where SE and rDiffAPI are defined ratios of solubility and diffusion coefficient in the presence and absence of EPO. SE decreased in the order of indomethacin, mefenamic acid, warfarin, piroxicam, furosemide, bezafibrate, and tolbutamide. The solubilizing effect was attributed to both ionic and hydrophobic interactions between drugs and EPO. The excellent solubilizing properties of EPO are highly promising for pharmaceutical development, and the data set provides first steps toward an understanding of drug-excipient interaction mechanisms.

In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions

As the number of applications for polymers in pharmaceutical development is increasing, there is need for fundamental understanding on how such compounds behave during tableting. This research is focussed on the tableting behaviour of amorphous polymers, their solid dispersions and the impact of hot-melt extrusion on the compaction properties of these materials. Soluplus, Kollidon VA 64 and Eudragit EPO were selected as amorphous polymers since these are widely studied carriers for solid dispersions, while Celecoxib was chosen as BCS class II model drug. Neat polymers and physical mixtures (up to 35% drug load) were processed by hot-melt extrusion (HME), milled and sieved to obtain powders with comparable particle sizes as the neat polymer. A novel approach was used for in-line analysis of the compaction properties on a rotary tablet press (Modul P, GEA) using complementary sensors and software (CDAAS, GEA). By combining ‘in-die’ and ‘out-of-die’ techniques, it was possible to investigate in a comprehensive way the impact of HME on the tableting behaviour of amorphous polymers and their formulations. The formation of stable glassy solutions altered the formulations towards more fragmentary behaviour under compression which was beneficial for the tabletability. Principal component analysis (PCA) was applied to summarize the behaviour during compaction of the formulations, enabling the selection of Soluplus and Kollidon VA 64 as the most favourable polymers for compaction of glassy solutions.

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets

This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms.

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing

FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the ‘peeling’ style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing.

Preparation of polymer-blended quinine nanocomposite particles by spray drying and assessment of their instrumental bitterness-masking effect using a taste sensor

Context: The development of taste-masking technologies for foods and drugs is essential because it would enable people to consume and receive healthy and therapeutic effect without distress.Objective: In the current study, in order to develop a novel method to prepare nanocomposite particles (microparticles containing bitter nanoparticles) in only one step, by using spray drying, a two-solution mixing nozzle-equipped spray dryer that we previously reported was used. The nanocomposite particles with or without poorly water-soluble polymers prepared using our spray-drying technique were characterized.Methods: (1) The organic solution containing quinine, a model of bitter compound and poorly water-soluble polymers and (2) sugar alcohol (mannitol) aqueous solution were separately flown in tubes and two solutions were spray dried through two-solution type spray nozzle to prepare polymer-blended quinine nanocomposite particles. Mean diameters of nanoparticles, taste-masking effect and dissolution rate of quinine were evaluated.Results: The results of taste masking by taste sensor suggested that the polymer (Eudragit EPO, Eudragit S100 or Ethyl cellulose)-blended quinine nanocomposite particles exhibited marked masking of instrumental quinine bitterness compared with the quinine nanocomposite particles alone. Quinine nanocomposite formulations altered the quinine dissolution rate, indicating that they can control intestinal absorption of quinine.Conclusion: These results suggest that polymer-blended quinine composite particles prepared using our spray-drying technique are useful for masking bitter tastes in the field of food and pharmaceutical industry.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterization.

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

FORMULATION AND EVALUATION OF TASTE MASK ORALLY DISPERSIBLE PARACETAMOL TABLET

Mostly the drugs are administered by oral route. Orally dispersible tablets are achieving importance when compared to novel oral drug delivery system. Orodispersible tablets are suitable for all age patients by masking the taste of drug. The objective of the present study was to optimize, formulate and evaluate orally dispersible tablet (ODT) of Paracetamol which disintegrates within few seconds in presence of saliva fluid by the use of super disintegrants. Paracetamol is widely used over-the counter analgesic (pain reliever) and antipyretic (fever reducer). It is a very bitter drug so the patients unable to take orally; hence their bitter taste were masked. ODTs Formulations were prepared by Direct Compression and wet granulation method by the use of superdisintegrants and taste masking (F7;F8) is done by Eudragit EPO. The developed formulations were evaluated in terms of weight variation, drug content, friability, thickness, hardness, disintegration and in vitro dissolution test. Stability study of optimized formulation was also carried out as per ICH guidelines. The effects of disintegrants as well as binders in different concentration on the release profile of paracetamol ODTs were studied. The studied parameters were found to be satisfactory for all formulations. Disintegration time for the formulations was found to be less than 40 seconds. Disintegration time for all ODTs decreased with increase in disintegrant concentration. ODTs prepared using Avicel possessed least disintegration time (11s), offered better dissolution profile than that of all the ODTs formulations. Accelerated studies proved that the optimized formulation was stable even after three months. Keywords: Orodispersible tablets, Paracetamol, Prosolv ODT; Eudragit EPO, physical characterization. in-vitro dissolution,

Microencapsulation of iron in a reversed enteric coating using spray drying technology for double fortification of salt with iodine and iron

AbstractPrevention of iron deficiency, the most widespread nutritional disorder, can be achieved by salt double fortification; however, iron addition requires the prevention of iron‐iodine interaction. For this purpose, reversed enteric coated iron‐containing microparticles were developed in this study.Microparticles were produced using either of two coating materials: Eudragit EPO and chitosan. Coating material solutions were loaded with increasing amounts of iron and then spray dried. Maximum payloads were established and functionality/morphology of microparticles was assessed. Microparticles were added into iodized salt with different moisture contents and adhesion and stability was measured during storage.Eudragit EPO is unsuitable for iron fortification, as even low payloads prevented solid particles formation. Chitosan was an effective iron coating as good functionality/morphology was achieved with loadings up to 25%. The best particles were spherical (∼10 µm average diameter) and retained the encapsulated iron at pH 7 and released it at pH 1. Chitosan microparticles can be properly attached to the surface of coarse salt when the initial moisture content of salt is 2.4%, and iodine retention after 12 weeks storage was 90% at 25C and 70% at 45C.Chitosan is suitable for producing an iron premix for stable salt double fortified with iodine and iron.Practical ApplicationsDouble fortification of salt with iodine and iron has been proved to be effective in reducing iron deficiency prevalence in India. Current fortification approaches use iron particles developed using an extrusion or fluidized bed agglomeration processes, to match the size and appearance of salt grains.However, in the developing world, the most consumed salt type is coarse salt. This fact imposes the need for developing iron microparticles that can be attached to the surface of coarse salt. Salt requires 2.4% moisture for good attachment. Iron microparticles must be stable in such environment. This can be achievable using reversed enteric coatings for avoiding the interaction of iodine and iron during salt preparation and storage.

Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters.

The aim of this article was to construct a T-ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature-composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)-Eudragit(®) EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10wt% FD-EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature-composition (T-ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid-solid curve in a F-H T-ϕ phase diagram. If extruded between the spinodal and liquid-solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F-H T-ϕ phase diagrams are valuable not only in the understanding drug-polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.