Search

Background Currently, the Bilayer tablets, Tablet in tablet and Inlay tablets composed of Glimepiride (GMP) and Pioglitazone (PGH) as immediate release part, and Metformin (MFH) as sustained-release part are available for the treatment of type II diabetes mellitus (T2DM). In these products, there is a possibility of the incomplete release of immediate release part (GMP and PGH) due to their entrapment into high viscosity gel barrier of MFH sustained-release part when drug product comes in contact with media. Therefore, the present study was aimed to deliver the above combination drugs in the form of hard gelatin capsules (as unit dosage form) containing MFH sustained-release (MFH-SR) pellets and immediate release pellets of PGH and GMP (PG-IR). Results The MFH-SR and GP-IR pellets, prepared by extrusion and spheronization technique, were optimized based on the drug content and % cumulative drug release. The MFH-SR pellets formulation (batch A6) has shown maximum drug content, and sustained-release of MFH similar to marketed glucophage tablet while, the GP-IR pellets formulation (batch B5) has displayed maximum drug contents and immediate release of GMP and PGH; thus, these batches were considered for further characterizations. The optimized MFH-SR and GP-IR formulations have shown particle sizes of 0.23 ± 0.0010 mm and 0.35 ± 0.0018 mm, respectively. Besides, the formulations exhibited good micromeritics properties. The in vivo pharmacokinetic study in rabbits has demonstrated comparable bioavailability of the drugs from pellets and the marketed formulations following oral administration. Further, the pellets were found to be stable for 6 months at 40 ± 2 °C/75% ± 5%RH. Conclusions The study results revealed that the multiparticulate systems with varied release profiles could be a promising approach to overcome drug release issues associated with the unit dosage forms.

The particles of phenytoin (Phe), a poorly water-soluble model drug, were bead-milled alone or co-milled with a hydrophilic waxy additive using an ultra cryo-milling technique in liquid nitrogen (LN2) to improve its dissolution properties. However, the micronized drug particles adhered and aggregated, resulting in poor handling in manufacturing processes such as blending or tableting. To improve the dissolution profile and powder properties of the drug simultaneously, the milled products were secondarily processed together with larger spherical particles by mechanical powder processing. These secondary products were composite particles with a core-shell structure, with fine drug particles adhered and deposited on the core, based on order mixing theory. As a core, three types/sizes of spherical pharmaceutical excipient particles were applied. The resultant composite particles produced much faster release profiles than just milled or co-milled mixtures. In addition, the composite particles showed good micromeritic properties depending on the size of the core particles. These results indicate that the ultra cryo-milling and subsequent dry composite mixing is a potential approach for developing drug particles with improved dissolution.

Black cumin seed oil (MBJH) ( Nigella sativa L .) is a well-known herb with pharmacology activities such as anticancer and anti-thrombocytopenia. The limitation of MBJH has poor absorption when using oral dosage form. The liquid SNEDDS (Self-nanoemulsifying drug delivery system) of MBJH as an alternative formulation. However, the disadvantage of liquid-SNEDDS of MJBH was the interaction between the active ingredients with soft gelatin capsules. Hence, this study proposed to develop solid-SNEDDS as a new formulation of MBJH. Solid-SNEDDS of MBJH was prepared from liquid-SEDDS of MBJH by adsorption to solid carrier method, consisting of aerosil and crospovidone as the adsorbent. The characterization of S-SNEDDS was determined by emulsification time and percent transmittance. Micromeritics properties of S-SNEDDS such as the angle of repose, bulk and tap density parameter, compressibility index, and Hausner ratio were measured before and after stored in stress condition (40 C ± 2 C and relative humidity of 75% ± 5% for 14 days). The result showed S-SNEDDS of MBJH with aerosil absorbent had better S-SNEDDS performance in both characteristics and micromeritics properties under stress conditions than crospovidone absorbent. In conclusion, the s-SNEDDS of black cumin oil by solid aerosil carrier method is promising for future research development of S-SNEDDS dosage form.

Introduction: Modifying natural polymers have imparted desirable properties making them suitable as pharmaceutical additives. Aim: This research work was to prepare pre-gelatinized breadfruit starch using acetone to reduce drying time and energy expended. The modified starch was evaluated as a disintegrant in paracetamol oral compacts. Methods: Starch from unripe mature bread fruit was pre-gelatinized, precipitated with acetone to reduce drying time. Native and pre-gelatinized starches were characterized for micromeritics, compatibility studies with test drug using Fourier Transform Infra-Red (FT-IR) and water interaction properties (viscosity, swelling power and hydration capacity). Paracetamol granules formed by wet granulation were compacted incorporating starches as disintegrant intragranularly, extragranularly and combining both methods. Disintegration and dissolution studies done. Results: Pre-gelatinization did not alter the native starch chemically and their pH were within pharmaceutical limits. The disintegration efficiency ratio (DER) for the P2 and P3 (tablet batches with pre-gelatinized starches) compared favourably with that of corn starch. Also, the dissolution kinetics of the breadfruit starches followed the Hixson Crowel’s model while that of reference corn starch was best described by the Higuchi kinetic model. Conclusion: Breadfruit starch is edible and the properties of its pre-gelatinized form as a disintegrant compares favourably with corn starch BP. It could be an good alternative as pharmaceutical excipient.

The Fluidized hot melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated using a low melting binder. The effect of the binder properties and concentrations on agglomerate growth mechanisms were studied in this research paper using this technique with the primary objective of improvement in the solubility and dissolution rate of efavirenz by melt-dispersion granulation employing meltable hydrophilic carrier and then to convert the melt dispersion into flowable and compressible dispersion granules to yield a rapidly dissolving tablet formulation. The Optimized concentrations of co-polymers like PEG 6000, PEG 4000, Gelucire 50/13, Gelucire 44/14, Poloxamer 188 and Poloxamer 407 in different ratios (i.e., 1:1, 1:2, 1:3 and 1:4) as meltable binder along with the drug were sprayed dropwise over lactose as diluent loaded into fluid bed chamber for the preparation of the granules of efavirenz and characterized for its micromeritical properties, DSC, XRD etc. The tablets prepared from the granules were evaluated for drug dissolution rate. The prepared granules were found to have excellent flow properties indicated by mean diameter D50:138µm, Carr’s index 13.92% and the drug content uniformity of 98.10%. XRD data exhibited partial loss of crystallinity as indicated by significantly less intensity of efavirenz peak in sample than pure efavirenz. Drug release from tablet was fast found 99.12% w/v within 30 minutes. Absence of Efavirenz endothermic peak at higher proportions of meltable binder reported by DSC data exhibited amorphous form of efavirenz led to complete solubilization and thus faster dissolution rate of efavirenz.

Objective: The present study was aimed to develop the formulation and in vitro evaluation of Orodispersible tablets by wet granulation method using Donepezil HCl as a model drug to enhance patient compliance. Methods: In the wet granulation method, a mixture of microcrystalline cellulose and hydroxypropyl methylcellulose were used along with superdisintegrants, i.e., croscarmellose sodium and crospovidone. The prepared granules were subjected to both pre and post-compression evaluation parameters including; FTIR spectroscopy, micromeritics properties, tablet weight variation, hardness, friability, drug content, disintegration time and in vitro drug release. Results: FTIR studies indicated that there was nointeraction between the drug and the excipients used. The formulation containing high concentration of crospovidone and mixture as the best formulation F2 based on in vitro drug release characteristics of tablet formulation. Conclusion: The results of this work suggested that orodispersible tablets of Donepezil hydrochloride with rapid disintegration time, fast drug release and good hardness can be efficiently and successfully formulated by wet granulation method.

The purpose of this investigation is to establish anti-diabetic activity relationship as well as efficiency of formulated guar gum matrix tablet using microencapsulated glibenclamide (GBLD). This research is an approach to utilize pharmaceutical excipients as an alternative hypoglycemic agent. In order to execute the objective, GBLD microspheres were formulated by emulsion solvent evaporation method using dichloromethane and methanol as solvent system which was transferred drop after drop into encapsulating medium i.e. liquid paraffin light. The formulated microspheres were exposed to various assessment parameters like drug entrapment efficiency, % yield, particle size distribution, and average particle size, the morphology of surface, dissolution study (in vitro) and micromeritics of prepared microspheres. By using these microspheres, matrix tablets were then prepared which were further evaluated for weight variation, thickness, friability, hardness, drug content, stability study, disintegration time, swelling index and dissolution (in vitro) studies were carefully carried out. Betwixt all the formulated microspheres GEM3 was found to best optimized with respect to evaluation parameters. The results obtained were found within the desired ranges where % yield 93.75%, drug entrapment efficiency 95.627% at 12th hour, and the average particle size was observed to be 179.4±0.12 µm. Then, by using the method of direct compression matrix tablets of optimized microspheres GEM3 were prepared and drug release (in vitro) was performed. The obtained results of performed parameters on matrix tableted microspheres were within the acceptable range according to IP guidelines. Out of all formulated matrix tableted microspheres, formulation GMT4 and GMT7 showed an in-vitro % drug release of 95.257 and 94.404 at 12th hour in pH 7.4 phosphate buffer.

The objective of present work was to develop fibroin-sodium alginate floating microspheres of felodipine (FD) showing modified release. Binary polymer system of fibroin-sodium alginate was used to prepare microspheres by spray drying technique. Thus, FD loaded microspheres obtained were evaluated for % drug content, % entrapment efficacy, particle size, micromeritics, FT-IR, DSC, XRD, floatability profile, mucoadhesion, in vitro drug release, and accelerated stability studies. The drug content of FD-loaded microspheres (F1–F5) was in the range of 68.55 ± 1.20 to 78.21 ± 0.54 and entrapment efficacy 45.93 ± 0.41 to 61.60 ± 0.72%. The particle size varied from 60.33 ± 0.64 to 66.87 ± 0.85 μm. Acceptable Carr’s compressibility index and angle of repose demonstrated excellent flowability of microspheres (F1–F5). The FT-IR showed no chemical interactions between FD and polymers. The DSC and XRD indicated that FD was partially crystalline in microspheres. Floating parameters for optimized batch F2 were floating lag time10–15 s and floating time > 12 h. Floating buoyancy is 96.51 ± 0.66%. The in vitro drug dissolution kinetics of optimized F2 batch in 0.1NHCl and FSSGF demonstrated % drug release up to 80.42 ± 0.86% in 0.1NHCl and 84.64 ± 0.30% in FSSGF following Peppas model. Electrostatic repulsion between polymers successfully enabled the design of FD-loaded floating microspheres by spray drying. Excellent floating profile and extended release for 12 h, as per USFDA guidelines, have been demonstrated by the fibroin-sodium alginate binary composite system. In the future, fibroin-sodium alginate scaffold can be successfully used for tailor-made floating and release profiles of drugs belonging to different solubility classes.

Background Sorbitan monostearate is a surfactant used in the food industry. It was proved as a penetration enhancer to metformin HCl via a paracellular pathway. It is solid at room temperature and has a low melting point. Therefore, it was selected, as a granulating agent for metformin HCl. Methods Multi-level factorial design was applied to determine the optimized formula for industrial processing. The selected formulations were scanned using an electron microscope. Differential scanning calorimetry was used to ascertain the crystalline state of a drug. A modified non-everted sac technique, suggested by the authors, was used to evaluate the in vitro permeation enhancement of the drug. To simulate the emulsification effect of the bile salt, a tween 80 was added to the perfusion solution. As a pharmacodynamic marker, blood glucose levels were measured in diabetic rats. Results The results showed that drug permeability increases in the presence of tween 80. Drug permeability from granules increased than that of the pure drug or pure drug with tween 80. The prepared granules decreased blood glucose levels of diabetic rats than the pure drug and drug plus tween 80. There was an excellent correlation between the results of the drug permeation percent in vitro and the dropping of blood glucose level percent in vivo. Conclusion Improving the drug permeation and consequently, the drug pharmacodynamic effect in addition to an excellent micromeritics property of the prepared drug granules showed the dual enhancement effect of the suggested industrial procedure. Therefore, we suggest the same industrial procedure for other class III drugs., Graphical Abstract

The specific surface and porosity of Belovo coal are determined. Coal samples undergo adsorption–structural analysis at the liquid-nitrogen temperature and at different relative partial pressures, on Sorbi N.4.1 and Termosorb TPD 400 instruments and also on the Micromeritics ASAP-2020 static vacuum system.

Reduced bioavailability of azelnidipine is related to its poor aqueous solubility and extensive first-pass metabolism, which hinder its efficacy. These problems were addressed by implementing (1) a liquisol technique for promoting the dissolution rate in a controlled-release manner and (2) a core-in-cup bucco-adhesive drug delivery system as an alternative to the oral route. A 33 factorial design was used to study the effects of polymer type (sodium carboxymethyl cellulose (CMC Na), chitosan, or Carbomer P940) concentration (5, 10 or 15 %) and preparation technique (simple mix, liquisol or wet granulation) on the dissolution and mucoadhesion of core-in-cup azelnidipine buccoadhesive tablets. Tablet micromeritics, swelling index, mucoadhesive strength and in vitro release were characterized. Statistical analyses of these factors show ed significant effects on the studied responses, where F#16 prepared by the liquisol technique and containing 15 % CMC Na was chosen with an overall desirability of 0.953.

In order to solve the problems of deficient CO2 adsorption sites on Zn/Co zeolitic imidazolate frameworks (ZIFs), Zn/Co ZIFs were thermally treated to promote physical adsorption sites on Zn-N and Co-N bonds and then impregnated with polyethyleneimine (PEI) to promote NH and NH2 chemical adsorption sites. The CO2 adsorption capacity detected on Micromeritics ASAP 2020C increased by 53% to 1.07 mmol/g at 298 K and 1 bar, when Zn/Co ZIF was treated at optimal temperature of 450 °C to obtain the maximum Me-N2 unsaturated adsorption sites. This was because of a partial cleavage of coordination bonds between Zn N, Co N, C N and C N along with dissociation of rationally free methyl groups in the framework ligands, which was supported on density functional theory (DFT) calculation. The Zn/Co ZIF treated at 450 °C and then impregnated with 40 wt% PEI exhibited the highest CO2 adsorption capacity of 1.82 mmol/g under the condition of at 298 K and 1 bar, which was 2.6 times higher than that of raw Zn/Co ZIF. In addition, this adsorbent is proved to be regenerable and stable during 9 cycle CO2 adsorption-desorption tests, therefore, PEI- thermally treated Zn/Co ZIF exhibits a very promising application in CO2 capture from flue gas and natural gas.

Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr’s index), Hauser’s ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr’s index 17.5%, Hauser’s ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350–2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation. Omeprazole magnesium powder did not change when subjected to stressful conditions of higher temperatures and relative humidity.

Penetration enhancement of metformin hydrochloride via its molecular dispersion in sorbitan monostearate microparticles is reported. This represents basic philosophy to maximize its entrapment for maximum penetration effect. Drug dispersion in sorbitan monostearate with different theoretical drug contents (TDC) were prepared. Products showed excellent micromeritics and actual drug content (ADC) increased by increasing TDC. The partition coefficient of the drug products showed huge improvement. This indicates the drug entrapped in the polar part of sorbitan monostearate as a special image which effects on the drug release. The drug permeation profiles from the different products are overlapped with nearly equal permeation parameters. The permeation results suggested the main driving force for improving the drug paracellular pathway is its dispersion in sorbitan monostearate and is independent of ADC. Pharmacodynamic of the products showed a significant improvement than the drug alone at p ˂ 0.05. ANOVA test indicated the insignificant pharmacodynamic difference between the low, middle, and high ADC of the products. An excellent correlation founded between the drug permeation and pharmacodynamic precents. Drug permeation driving force via the paracellular pathway is its entrapment in sorbitan monostearate and independent on ADC. The technique is simple and the products had excellent micromeritics.

The novel solvent-free process to formulate long-acting microparticles of tetracycline hydrochloride (TH) using hot melt extrusion granulation process coupled with size reduction using comil for the treatment of periodontitis was investigated using hydrogenated castor oil (HCO) as hydrophobic matrix former. The microparticles were characterized for micromeritics, drug diffusion, SEM studies, and stability analysis by DSC, FTIR, and proton NMR. Xanthan gum gel was used as delivery vehicles to administer microparticles inside periodontal pockets. The microparticles were sterilized using gamma radiation; delivery vehicle was sterilized using gamma radiation and autoclave process. Microparticles were evaluated for microbial load as per compendial guidelines. Optimized composition was evaluated for clinical parameters such as plaque index, gingival index, probing pocket depth, and clinical attachment level. Based on the statistical analysis of the data, the micromeritic properties and drug diffusion profiles vary based on the concentration of HCO in the formulation. SEM images reflect the surface properties prior and post drug diffusion studies, which indicates that release takes place predominantly by diffusion of TH through HCO matrix. DSC studies indicate no change in the respective spectra of initial and stability samples. FTIR studies indicate possibility of hydrogen bonding. Proton NMR data suggests characteristic peaks of TH being retained in the stability samples, indicating stable composition. Gamma radiation has led to significant reduction in viscosity of xanthan gum solution over autoclave. Clinical studies indicated statistical improvements in the formulation compared to baseline results, indicating the efficacy of the formulation in the treatment of periodontitis.

The current study was designed to convert the poloxamer (PLX) into thiolated poloxamer (TPLX), followed by its physicochemical, biocompatibilities studies, and applications as a pharmaceutical excipient in the development of tacrolimus (TCM)-containing compressed tablets. Thiolation was accomplished by using thiourea as a thiol donor and hydrochloric acid (HCl) as a catalyst in the reaction. Both PLX and TPLX were evaluated for surface morphology based on SEM, the crystalline or amorphous nature of the particles, thiol contents, micromeritics, FTIR, and biocompatibility studies in albino rats. Furthermore, the polymers were used in the development of compressed tablets. Later, they were also characterized for thickness, diameter, hardness, weight variation, swelling index, disintegration time, mucoadhesion, and in vitro drug release. The outcomes of the study showed that the thiolation process was accomplished successfully, which was confirmed by FTIR, where a characteristic peak was noticed at 2695.9968 cm−1 in the FTIR scan of TPLX. Furthermore, the considerable concentration of the thiol constituents (20.625 µg/g of the polymer), which was present on the polymeric backbone, also strengthened the claim of successful thiolation. A mucoadhesion test illustrated the comparatively better mucoadhesion strength of TPLX compared to PLX. The in vitro drug release study exhibited that the TPLX-based formulation showed a more rapid (p &lt, 0.05) release of the drug in 1 h compared to the PLX-based formulation. The in vivo toxicity studies confirmed that both PLX and TPLX were safe when they were administered to the albino rats. Conclusively, the thiolation of PLX made not only the polymer more mucoadhesive but also capable of improving the dissolution profile of TCM.

Purpose Traditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery. Methods Wet-sieving and spray-congealing were employed as innovative techniques to evaluate the impact of engineering on the particle properties of D-mannitol. To that end, the resulting powders were characterized concerning their solid-state, micromeritics and flowability. Afterwards, the engineered carrier particles were blended with inhalable size beclomethasone dipropionate to form low dose (1 wt%) DPI formulations. The in vitro aerosolization performance was evaluated using the NEXThaler®, a reservoir multi-dose device. Results Wet-sieving generated D-mannitol particles with a narrow particle size distribution and spray-congealing free-flowing spherical particles. The more uniform pumice particles with deep voids and clefts of wet-sieved D-mannitol (Pearl300_WS) were beneficial to drug aerosolization, only when used in combination with a ternary agent (10 wt% of ‘Preblend’). When compared to the starting material, the spray-congealed D-mannitol has shown to be promising in terms of the relative increase of the fine particle fraction of the drug (around 100%), when used without the addition of ternary agents. Conclusions The wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose.

Background: Pectin, a naturally occurring polysaccharide is more than a food additive and has got amazing properties as a gelling agent and as a binder. Objective: The current research entails the extraction and identification of pectin from peels of selected fruits mango (Magnifera indica) and banana (Musa paradisiaca) by direct heating and using alcohol as precipitating agent. The potential of pectin as a binding agent in tablet formulation was evaluated by screening its micromeritics and post compression properties. Method: quadruple formulations of ibuprofen with crude peel pectin extracted from mango and banana in concentration of 50, 75, 100 and 125 mg respectively were employed in the tablet manufacture process by wet granulation method. Results: Successful formulation of tablet was done with the extracted pectin from the two fruit peels. The micromeritics properties showed good binding and flowing properties. An increase in concentration of pectin increased the hardness and also the dissolution of tablets up to a certain extent. The disintegration time was suitable for all formulations. Conclusion: It was concluded that pectin extracted from mango and banana peels can be used as a super disintegrating agent in pharmaceutical formulations, where needed.

Rheology is also involved in the mixing and flow of materials, their packaging into containers, and their removal prior to use. In the field of pharmacy, micromertics has become an important area of study because it influences a large number of parameters in research, development, and manufacturing of dosage forms such as suspension to be reconstituted, tablet, and capsule. The content uniformity of a drug in a solid dosage form, particularly low dose and highly potent drugs, can also be affected by the particle size and size distribution of a drug. The simplest definition of particle size diameters is based on the assumption that particles are spherical. Mode diameter represents the particle size occurring most frequently in a sample; it is used far less frequently than mean and median diameter. The chapter discusses microscopy, sieving, and sedimentation methods. The size distribution and the surface area of powders are the two fundamental properties of any collection of particles.

In current times the utilization of the natural starches in various aspects like as pharmaceutical, biomedical, food materials, etc. due to their uniqueness properties. Assam bora rice starch is a promising biopolymer as well as bio-carrier in different aspects. Natural starch as well as modified starch was being used abundantly as natural polymers in different drug delivery systems. The prime advantages of using natural starches are low cost, easily available, renewability, etc. Starch obtained from Assam bora rice is having potential applications in pharmaceutical industries such as excipients and binder and disintegrates in tablet formulations, as an active drug carrier in nano, microformulations, and controlled drug delivery formulations. Assam bora rice starch as a native starch is having maleate particles which are often used for drug delivery carrier in the field biomedical application. The reasons behind this were due to their non-toxicity, biocompatibility, and inexpensive nature. In this chapter, we specially focus on Assam bora rice starch to profile its different applications along with physicochemical and powder flow properties which drastically affect the compactness of the starch granules.

Recent studies have shown great interest toward heavy metal removal due to its hazardous and non-biodegradable properties. Many approaches have been used for this purpose and one of them is adsorption. In this study, several experiments were carried out to investigate the feasibility of factory tea waste as a biosorbent in a fixed-bed adsorption column for heavy metal removal (zinc and copper) in wastewater. The results highlighted that zinc has better performance compared to copper in terms of the effect of initial ion concentration, pH value, and the mixed ions with respect to the removal efficiency. Zinc showed higher removal efficiency and adsorption capacity at the initial metal ion concentration of 200 mg/L, which are 99.21% and 39.68 mg/mg compared to copper. Meanwhile, for the effect of pH values and mixed ion concentration, zinc also showed slightly higher removal efficiency which are 99.91% and 98.47%, respectively compared to copper. However, both zinc and copper showed a better fit to the Langmuir isotherm. The factory tea waste was characterized using Micromeritics ASAP 2020 instrument and results showed that the factory tea waste biosorbent consists of mesopores with the diameter and width of 4.85205 and 2.546985 nm, respectively. Objectius de Desenvolupament Sostenible::9 - Indústria, Innovació i Infraestructura

Cycloserine, a high dose anti-tuberculosis agent, possesses poor flow properties and compression behaviour. The present study was aimed at improving the flowability, packing properties and compressibility of Cycloserine by spherical crystallization. Cycloserine was dissolved in a water and crystallised by pouring into anti-solvent, 1-Butanol, in presence of ethyl acetate which acts as a bridging liquid for formation of agglomeration. Further, spherical agglomeration process for Cycloserine was statistically optimized using the central composite design, keeping the ‘rate of stirring’ and ‘amount of bridging liquid’ as an independent factors and average particle size as the response. Optimized batch of Cycloserine spherical agglomerates (Cyc-SA) was further evaluated for sieve analysis, solid state characterization studies and compaction behaviour (Kawakita analysis and Heckel study). The uniform spherical agglomerates were revealed in microphotographs of scanning electron microscopy while no chemical alteration in the Cycloserine was indicated by X-Ray powder diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy during the crystallization. The excellent flow properties of Cyc-SA were demonstrated by Carr's index, Hausner ratio and Kawakita parameters as compare to plain drug. The enhanced particle size and uniform distribution of agglomerates have also contributed to improve flow properties of Cycloserine. Similarly, Heckel parameters like mean yield pressure and yield strength displayed superior compressibility of Cyc-SA. Thus, spherical crystallization would be interesting technique for improving processability of high dose drug like Cycloserine.

The present study was designed to determine the applicability of a newly derived dimensionless number precipitation parameter, "supersaturation holding capacity (SHC)" in development of amorphous solid dispersion (ASD) of a rapidly crystallizing drug, nisoldipine. Also, ASD preparation from lab scale formulation technique to scalable spray drying technique followed by oral bioavailability study was demonstrated. Solution state screening of polymers was performed by determining nucleation induction time (tin) and SHC. With screened polymers, lab scale ASDs of nisoldipine were prepared using rotary evaporation (solvent evaporation) method, and the optimized stable ASDs were scaled up by spray drying. The ASDs were characterized by DSC, PXRD, and FTIR for amorphous nature and evaluated for apparent solubility, dissolution, and solid-state stability improvement. The spray dried ASDs were additionally evaluated for micrometric properties and oral bioavailability study.PVP grades demonstrated superior crystal growth inhibition properties (with 2-4-fold enhancements in SHC). ASDs prepared by both lab scale and scale-up technique using PVP stabilized the amorphous nisoldipine via antiplasticization effect that maintained the stability under accelerated stability conditions (40 °C/75% RH) for 6 months. Additionally, FTIR study confirmed the role of intermolecular interactions in amorphous state stabilization of PVP-based solid dispersions. PVP-based spray dried ASDs improved the apparent solubility 4-fold for PVP K17 and more than 3-fold for remaining spray dried ASDs. The enhanced solubility was translated to improved dissolution of the drug when compared with crystalline and amorphous form complementing the outcome of the solution state study. The spray dried ASD showed 2.3 and 3-fold the improvement in Cmax and AUC (0-24 h) respectively when compared with crystalline nisoldipine during oral bioavailability study which highlights the significance of SHC parameter of polymers. The spray dried ASD has shown improved micromeritics properties then crystalline nisoldipine in terms of flow behavior.This unique study provides a rational strategy for selection of appropriate polymer in development of ASDs that can tackle both precipitation during dissolution and amorphous state stabilization in solid state and also considers the SHC in scale-up study. Graphical abstract.

Nifedipine has poor aqueous solubility which limits its oral absorption as unit formulation. This limitation was acted through multiparticulate pulsatile systems for the treatment of angina pectoris. Initially, solid dispersions of nifedipine (NF) using sodium starch glycolate (SSG) and guar gum (GG) in 1:1 and 1:2 ratios were processed by kneading technique. Solution layering technique was employed to coat the solid dispersions on non-pareil sugar spheres (∼450 µm) to obtain immediate (NMP 1 and 2) and controlled release pellets (NMP-3 and 4). Controlled release pellets were further coated with Eudragit L100 and RS100 to achieve pulsatile pellets (NMPP-1 to 5). Pellets were subjected to saturation solubility, FTIR, DSC, micromeritics, SEM, drug content, drug release, pharmacokinetic and stability studies. By means of solid dispersions, solubility of NF was increased by 130-folds due to encompassing ordered interparticle mixing of NF and carriers. Significant interactions between NF and carriers were not demonstrated in FTIR spectra as well as in DSC thermograms. Fluidization process again proved its supremacy in producing defined spherical shaped pellets with desired micromeritics. Solution layering process resulted with high drug content (81–94.2%) and maximum drug was released by end of 12 h with 6 h lag phase. Suitable pharmacokinetic parameters were moderated by immediate (NMP) and pulsatile pellets (NMPP) as Cmax of 820 ng/mL for NMP-2 and 360.8 ng/mL for NMPP-5 at 5 and 16 h respectively. Increased pharmacokinetics and bioavailability were the result of linear increase in solubility of NF with solid dispersions. The pulsatile formulations were physicochemically intact over a period of time. Thus, multiparticulate systems of NF had demonstrated their applicability in chronotherapy of circadian based ailments. Keywords: Angina, Circadian, Multiparticulates, Non-pareil, Solid dispersion, Solution-layering

Background: Blood-brain permeability is the primary concern when dealing with the biodistribution of drugs to the brain in neurological diseases. Objective: The purpose of the study is to develop the nanoformulation of Epigallocatechin gallate (EGCG) in order to improve its bioavailability and penetration into the brain. Methods: EGCG loaded Solid Lipid Nanoparticles (SLNs) have been developed using microemulsification method and pharmacological assessments were performed. Results: Surface morphology and micromeritics analysis showed the successful development of EGCG loaded solid lipid nanoparticles with an average size of 162.4 nm and spherical in shape. In vitro release studies indicated a consistent and slow drug release. Pharmacological evaluation of SLN-EGCG demonstrated a significant improvement in cerebral ischemia-induced memory impairment. Conclusion: The results indicate that the EGCG loaded SLNs provide a potential drug delivery system for improved delivery of EGCG to the brain, hence, enhancing its brain bioavailability.

Granular activated carbons (GACs) were used to separate carbon dioxide (CO2) from N2−CO2 feed gas mixture employing a fixed bed column. Two grades of GAC (GAC-1 and GAC-2) were used as an adsorbents. The adsorbents were characterized using Micromeritics ASAP surface analyzer and a scanning electron microscope. The parameters considered for examining the breakthrough responses of GACs were the initial concentration of CO2 in feed, temperature, and feed flow rate. It was observed that breakpoint time decreases with increased column temperature and with the gas feed rate for GAC-1 and GAC-2. For both types of activated carbons, the breakthrough time (tb) slightly decreases with increased initial CO2 concentration (vol. %) from 1% to 2% in feed. It was suggested that longer breakthrough time contributes to a higher adsorption capacity of an adsorbents. The adsorption breakthrough occurs early for GAC-2 compared with GAC-1 when the bed was subjected to the same temperature of 25 °C because of the superior surface characteristics of GAC-1. A longer breakthrough time of 1640 sec for GAC-1 was observed compared with a slower breakthrough time of 760 s for GAC-2 at a constant bed temperature of 25 °C subjected to a feed rate of 3 L/min (Cfeed = 5%). It was concluded that GAC-1 breakthrough was delayed compared with that of GAC-2 when the column was controlled to the same initial concentration of CO2 in the feed. The breakthrough periods of 960 s and 270 s were observed at an initial CO2 concentration of 2% in feed for GAC-1 and GAC-2, respectively. The maximum CO2 adsorption capacity of 25.39 g/kg adsorbent was estimated at a CO2 partial pressure of 0.048 bars for GAC-1.

Objective: The aim of the present study was to formulate and optimize famotidine loaded micro balloons for enhancing bioavailability, increasing gastric residence time of drug and to achieve sustained release in the stomach. Methods: Microballoons were prepared using emulsion solvent diffusion method using HPMC K4M as the polymer. All the formulated microspheres were subjected to various evaluation parameters such as % drug entrapment, micromeritics properties, % buoyancy and in vitro drug release studies. The formulation was optimized using 3 2 full factorial design. Optimized formulation was subjective to in vivo floating (X-ray) and in vivo antiulcer studies. Results: The microballoons were smooth and spherical in shape and were porous in nature due to hollow cavity. Sustained/controlled release of drug was observed for more than 12 h. based on the results of % drug entrapment, in vitro drug release and % buoyancy studies, formulation F6 was selected as optimized formulation. The release kinetics of optimized formulation followed Higuchi model and mechanism of release was non-Fickian diffusion. Examination of the X-ray radiographic images taken during the study indicated that the optimized formulation remained buoyant and uniformly distributed in the gastric contents for a long period. In ethanol-induced ulcer model, drug-loaded microballoons treated group showed significant ulcer protection index of 83.26% as compared to the marketed brand of famotidine 76. 09% and untreated control group. Conclusion: Famotidine-loaded floating micro balloons were successfully prepared and prove to be useful for the prolonged gastric residence of the drug, better bioavailability, patient compliance and anti-ulcer activity.

Quetiapine fumarate has possessed low solubility and extremely poor bioavailability, which restricts its oral administration. In order to address this concern, microemulsification technique was envisaged. Solubility of quetiapine was assessed in various liquid vehicles (oils, surfactants and cosurfactants) for the selection of carriers in self microemulsifying drug delivery system (SMEDDS) formulation. Microemulsion region was identified from the pseudoternary phase diagram. Quetiapine was loaded in preconcetrates of the predetermined microemulsion region. Quetiapine loaded SMEDDS were characterized for FTIR, pH, viscosity, zeta potential, and evaluated for drug content, in-vitro dissolution, in-vitro diffusion, and ex-vivo permeation. Optimized liquid SMEDDS were renewed into S-SMEDDS by adsorption and melt granulation technique. Formulated S-SMEDDS were characterized for micromeritics, DSC, SEM, and evaluated for drug content, reconstitution time, drug release, stability and anti-psychotic activity in animals for amphetamine induced stereotypy and swimming normalization test. The formulations of O11, O13, C6 and C10 liquid SMEDDS had shown drug release of 92, 94.16, 68.59 and 55.03% respectively at the end of 1 h. S-SMEDDS exhibited good micromeritics with a drug content of 80 to 90% and released drug up to 96%. AO13 of S-SMEDDS had 1.2 years of shelf life and exhibited better anti-psychotic activity owing to enhanced biomembrane permeation in the presence of tweens as surfactants. The spontaneous formation of microemulsion from adsorption based S-SMEDDS resulted in hasty drug release. Thus the results of the study indicated that self microemulsification of quetiapine and subsequent solidification is the better alternative in affording optimal pharmacotherapy of psychosis.

A Central Composite Rotatable Design (CCRD) was applied to statistically optimized lipospheres (LS) formulated for enhancing the pharmacokinetics of co-administered Ivabradine and Nebivolol as well as improving the patients’ compliance. The lipospheres (LS) were prepared by simple melt emulsification technique and impact of formulation variables (Carnauba wax, Beeswax, and surfactant) on percentage yield (Y1), IVB-release (Y2) and NEB-release (Y3) was statistically investigated. The numerical optimization technique was adopted to select optimized lipospheres (OL) which were then subjected to a comparative in vivo pharmacokinetic analysis against commercially available brands. The physicochemical analysis of LS was performed by FTIR, DSC and x-ray powder diffractometry (XRD). Lipospheres were also analysed for micromeritics, zeta potential, size, and morphology. The spherical, smooth surface, free-flowing LS having zeta potential of −40 to −60 mV and size-range of 10–50 µm were successfully formulated. The physicochemical analysis demonstrated a complete lack of drugs interaction with lipids carriers, and p-XRD showed a transformation of crystalline drugs to amorphous form. The outcomes for Y1 (38–88%), IVB-release (47–96%) and NEB-release (38–88%) followed polynomial quadratic model. The pharmacokinetics analysis of LS showed a significantly decreased Cmax of IVB (39.29 ± 6.39), NEB (56.69 ± 3.73) with an effectively raised Tmax (13.41 h for IVB and 14.53 h for NEB) as compared to IVB (49.67 ± 5.26 ng/mL) and NEB (71.32 ± 4.57 ng/mL) of commercial brands. Moreover, an expressively increased half-life (17hr for IVB, 19 hr for NEB), AUC0-24 (8121 for IVB, 11,368 for NEB) and mean residence time for IVB and NEB indicated the accomplishment of greater bioavailability of drugs released from LS. Conclusively, such an innovative idea of combination loaded LS of IVB, and NEB would convincingly bring an effective management of chronic cardiovascular complications by maintaining the plasma drugs concentration for a prolonged time.

Advantage of spray drying technique over the conventional surface adsorption technique for co-formulation of solid SNEDDS (S-SNEDDS) of curcumin (CRM) and duloxetine (DXH) is discussed. Liquid SNEDDS were prepared using castor oil (20% w/w), Tween-80 (40% w/w) and Transcutol® P (40% w/w) as oil, surfactant and co-surfactants containing both CRM and DXH. S-SNEDDS were formulated by adsorption of liquid SNEDDS onto porous hydrophilic and hydrophobic carriers through spray drying and surface adsorption techniques. The percentage drug loading for CRM and DXH in optimized L-SNEDDS was 87.22 ± 1.87 and 92.32 ± 0.19%, mean droplet size, 113.14 ± 1.14 nm; polydispersity index, 0.20 ± 0.026, and zeta potential − 13.2 mV, respectively. Prepared formulation was evaluated for parameters such as, oil adsorption tendency, micromeritic characteristics, disintegration and dissolution behaviour to identify suitable carrier for conversion of L-SNEDDS into S-SNEDDS. Among the carriers used, Syloid® 244FP revealed highest oil adsorption capacity. Spray drying of L-SNEDDS using Syloid® 244FP as carrier further improved micromeritic properties with lower angle of repose (22.18 ± 0.22°), higher flow rate (4.33 ± 0.26 g/s), lower true (1.23 ± 0.22 g/cm3), bulk (0.202 ± 0.05 g/cm3) and tapped density (0.216 ± 0.07 g/cm3). In vitro dissolution and ex-vivo permeation studies revealed non-significant (P > 0.05) drugs' release from S-SNEDDS powders/tablets viz-a-viz their L-SNEDDS formulation. SNEDDS were found to be remarkably superior over the unprocessed drugs in their dissolution and permeation studies. They were found to be stable in terms of droplet size, dissolution pattern, tablet hardness and assay when subjected to stability testing. Scanning Electron Microscopy, Differential Scanning Calorimetry and powder X-ray diffraction studies revealed that crystalline drugs were converted to their amorphous state in the SNEDDS formulations. Spray drying technique has, therefore proved to distinctly improve the micromeritics and biopharmaceutical attributes in the co-formulation of curcumin and duloxetine S-SNEDDS.

The aim of present attempt deals with preparation of binary dispersion of sericin, waste of sericulture industry in order to enhance solubility and dissolution of poorly soluble drugs. Solid dispersions (SDs) of BCS-II drugs were prepared by spray drying, solvent evaporation, ball milling and physical mixing in ratio of drug:sericin (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3). Further, SDs were investigated by solubility, ATR-FTIR, XRD, DSC, micromeritics and tablettability, surface morphology and in-vitro dissolution. Results demonstrated that, sericin improves solubility of drugs by 8-10 fold. The ATR-FTIR showed the slight shifting/broadening of principle peaks corresponding to NH and OH. Spray dried (1:2w/w) SDs showed maximum reduction in crystallinity of drugs indicating drug was molecularly distributed and was in amorphous state. Spray dried SDs of meloxicam showed better compressibility and compactibility. The microphotograph of spray dried SDs of lornoxicam and meloxicam showed bowl shaped and blend of bowl and spherical particles respectively, while spray dried SDs of felodepine showed spherical shape. The spray dried SDs (1:2w/w) displayed better dissolution performance than other methods Conclusively, sericin offers a hydrophilic matrix to deliver poor water soluble drugs and its aerodynamic shape may show a great potential for various drug deliveries.