Reduction In Drug Crystallinity Research Articles

Precision drug delivery through methotrexate and tofacitinib citrate encapsulated mesoporous silica scaffold

Background: Advancements in drug delivery aim to enhance outcomes while reducing adverse effects. Mesoporous silica nanoparticles (MSN) offer potential for targeted delivery due to their unique properties, including ordered pore structure, large surface area, and biocompatibility. Methods: MSN were synthesized using tetraethyl orthosilicate (TEOS) and Pluronic F127, then amine-functionalized with 3-aminopropyltriethoxysilane. Methotrexate and tofacitinib citrate were loaded via incipient wetness impregnation. Characterization included FTIR, particle size analysis, TEM, SEM, DSC, XRD, and BET analysis. Results: FTIR confirmed surface modification. Particle size analysis showed nanoscale dimensions. TEM and SEM depicted ordered mesoporous structures. DSC indicated drug crystallinity and MSN amorphism. XRD revealed reduced drug crystallinity in MSN. BET analysis demonstrated high MSN surface area and pore volume. Drug-loading efficiency was 62.44%. Conclusion: Comprehensive synthesis and characterization of MSN for targeted drug delivery were achieved successfully, highlighting their potential in overcoming conventional therapy limitations.

Enabling superior drug loading in lipid-based formulations with lipophilic salts for a brick dust molecule: Exploration of lipophilic counterions and in vitro-in vivo evaluation

Lipid-based formulations (LbFs) are an extensively used approach for oral delivery of poorly soluble drug compounds in the form of lipid suspension and lipid solution. However, the high target dose and inadequate lipid solubility limit the potential of brick dust molecules to be formulated as LbFs. Thus, the complexation of such molecules with a lipophilic counterion can be a plausible approach to improve the solubility in lipid-based solutions via reducing drug crystallinity and polar surface area. The study aimed to enhance drug loading in lipid solution for Nilotinib (Nil) through complexation or salt formation with different lipophilic counterions. We synthesized different lipophilic salts/ complexes via metathesis reactions and confirmed their formation by 1H NMR and FTIR. Docusate-based lipophilic salt showed improved solubility in medium-chain triglycerides (∼7 to 7.5-fold) and long-chain triglycerides (∼30 to 35-fold) based lipids compared to unformulated crystalline Nil. The increased lipid solubility could be attributed to the reduction in drug crystallinity which was further confirmed by the PXRD and DSC. Prototype LbFs were prepared to evaluate drug loading and their physicochemical characteristics. The findings suggested that structural features of counterion including chain length and lipophilicity affect the drug loading in LbF. In addition, physical stability testing of formulations was performed, inferring that aliphatic sulfate-based LbFs were stable with no sign of drug precipitation or salt disproportionation. An in vitro lipolysis-permeation study revealed that the primary driver of absorptive flux is the solubilization of the drug and reduced amount of lipid. Further, the in vivo characterization was conducted to measure the influence of increased drug load on oral bioavailability. Overall, the results revealed enhanced absorption of lipophilic salt-based LbF over unformulated crystalline Nil and conventional LbF (drug load equivalent to equilibrium solubility) which supports the idea that lipophilic salt-based LbF enhances drug loading, and supersaturation-mediated drug solubilization, unlocking the full potential of LbF.

Modification of physicochemical properties of chitosan to improve its pharmaceutical and agrochemical potential applications

Chitosan has received much more attention as a functional biopolymer with applications in pharmaceuticals, agricultural, drug delivery systems and cosmetics.The objectives of present investigation were to carry out modification of chitosan for enhancement of aqueous solubility, which will impart increased solubility and dissolution rate of poorly soluble drug itraconazole (ITZ) and also evaluate the modified chitosan for soyabean seed germination studies.The modification of chitosan was accomplished through the antisolvent precipitation method; employing five carboxylic acids. The resulting products were assessed for changes in molecular weight, degree of deacetylation, solubility and solid state characterization. Subsequently, the modified chitosan was complexed with itraconazole using the co-grinding technique. The prepared formulations were evaluated for solubility, FTIR (Fourier-transform infrared spectroscopy), PXRD (Powder X-ray diffraction), in-vitro dissolution studies. Furthermore the effect of modified chitosan has been evaluated on soybean seed germination.Results demonstrated that, modified chitosan improves self and solubility of itraconazole by six folds. As there was increased degree of deacetylation of chitosan leads to improvement in solubility. The results of FTIR showed the slight shifting of peaks in co-grind formulations of itraconazole. Formulations showed reduction in crystallinity of drug which leads to enhancement in dissolution rate as compared to pure itraconazole. Retention of property of seed germination was observed with modified chitosan at optimum concentration of 3 % w/v, with benefit of enhanced aqueous solubility of chitosan.This positive result paves the way for the advancement of pharmaceutical and agrochemical products employing derivatives of chitosan.

The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

DOPE/CHEMS-Based EGFR-Targeted Immunoliposomes for Docetaxel Delivery: Formulation Development, Physicochemical Characterization and Biological Evaluation on Prostate Cancer Cells

Docetaxel (DTX) is a non-selective antineoplastic agent with low solubility and a series of side effects. The technology of pH-sensitive and anti-epidermal growth factor receptor (anti-EGFR) immunoliposomes aims to increase the selective delivery of the drug in the acidic tumor environment to cells with EFGR overexpression. Thus, the study aimed to develop pH-sensitive liposomes based on DOPE (dioleoylphosphatidylethanolamine) and CHEMS (cholesteryl hemisuccinate), using a Box-Behnken factorial design. Furthermore, we aimed to conjugate the monoclonal antibody cetuximab onto liposomal surface, as well as to thoroughly characterize the nanosystems and evaluate them on prostate cancer cells. The liposomes prepared by hydration of the lipid film and optimized by the Box-Behnken factorial design showed a particle size of 107.2 ± 2.9 nm, a PDI of 0.213 ± 0.005, zeta potential of -21.9 ± 1.8 mV and an encapsulation efficiency of 88.65 ± 20.3%. Together, FTIR, DSC and DRX characterization demonstrated that the drug was properly encapsulated, with reduced drug crystallinity. Drug release was higher in acidic pH. The liposome conjugation with the anti-EGFR antibody cetuximab preserved the physicochemical characteristics and was successful. The liposome containing DTX reached an IC50 at a concentration of 65.74 nM in the PC3 cell line and 28.28 nM in the DU145 cell line. Immunoliposome, in turn, for PC3 cells reached an IC50 of 152.1 nM, and for the DU145 cell line, 12.60 nM, a considerable enhancement of cytotoxicity for the EGFR-positive cell line. Finally, the immunoliposome internalization was faster and greater than that of liposome in the DU145 cell line, with a higher EGFR overexpression. Thus, based on these results, it was possible to obtain a formulation with adequate characteristics of nanometric size, a high encapsulation of DTX and liposomes and particularly immunoliposomes containing DTX, which caused, as expected, a reduction in the viability of prostate cells, with high cellular internalization in EGFR overexpressing cells.

Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate.

Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5–25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion—surface utilization factor—were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing.

Design and optimization of pH-sensitive Eudragit nanoparticles for improved oral delivery of triclabendazole

Design of Experiments (DoE) techniques were used to identify and optimize the parameters involved in the formulation of triclabendazole pH-sensitive Eudragit® nanoparticles (NPs). Using a Placket Burmann design, Eudragit® E, Eudragit® RS, and two stabilizers (PVP and PVA) were evaluated for NPs formulation by nanoprecipitation. Based on the screening results, Eudragit E 100® and PVP were selected as excipients, and their levels were studied and optimized using a central composite design, obtaining an optimum nanoparticulated system with a Size of 240 nm, a PDI of 0.420, and a ZP of 46.3 mV. Finally, a full characterization of the optimum system was carried out by XRD, DSC, equilibrium solubility, and dissolution rate in biorelevant mediums. As observed in XRD and DSC, the nanoencapsulation process produced a remarkable reduction in drug crystallinity that improved drug solubility and dissolution rate. Although more than 90% of TCBZ was dissolved in acidic mediums at 10 min, no increase in solubility or dissolution rate was observed in simulated saliva. Consequently, the development of pH-sensitive Eudragit® NPs would be a promising strategy in developing an immediate gastric release TCBZ formulation for oral delivery.

Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances.

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.

A Novel Prototype Device for Microencapsulation of Benznidazole: In Vitro/In Vivo Studies.

This study was aimed to design a simple and novel prototype device for the production of polymeric microparticles. To prove the effectiveness of this device, benznidazole microparticles using chitosan as carrier and NaOH, KOH, or SLS as counter ions were used. For comparison, benznidazole microparticles were prepared by the conventional dripping technique (syringe and gauge) using the same excipients. Microparticles were characterized in terms of encapsulation efficiency, particle shape, size and surface topography, crystallinity characteristics, thermal behavior, and dissolution rate. Then, the pharmacokinetic parameters were evaluated after the oral administration of the microparticles to healthy Wistar rats. The prepared formulations, by means of this device, showed good drug encapsulation efficiency (> 70%). Release studies revealed an increased dissolution of benznidazole from chitosan microparticles prepared using the novel device. It achieved more than 90% in 60min, while those of the conventional microparticles and raw drug achieved 65% and 68%, respectively, during the same period. Almost spherical benznidazole microparticles with a smooth surface and size around 10-30μm were observed using scanning electron microscopy. Thermal analysis and X-ray diffraction studies suggested a partial reduction of drug crystallinity. Moreover, the relative oral bioavailability of the novel benznidazole microparticles showed that the area under the curve for the microencapsulated drug was 10.3 times higher than the raw drug. Thus, these findings indicate that the designed glass prototype device is a useful alternative to formulate benznidazole polymeric microparticles with improved biopharmaceutical properties and could be useful for other therapeutic microparticulate systems.

Imiquimod-oleic acid prodrug-loaded cream reduced drug crystallinity and induced indistinguishable cytotoxicity and apoptosis in mice melanoma tumour

In the present investigation, imiquimod (IMQ) was coupled to oleic acid (OLA; IMQ-OLA) to synthesise prodrug to reduce crystallinity that later amalgamated with oil-in-water (o/w) emulsion cream (IMQ-OLA cream) for the treatment of melanoma tumour. The synthesis of IMQ-OLA prodrug was verified by FT-IR, 1HNMR and mass spectroscopy. The crystalline lattice of IMQ was transformed to somewhat amorphous structure in IMQ-OLA prodrug. IMQ-OLA cream retained 35.6% of IMQ within skin, significantly (p < 0.05) higher than 22.3% and 10.6% retained by marketed IMQ cream and IMQ solution, respectively. IMQ-OLA cream suppressed the melanoma tumour to 70.3 mm3 in C57BL6J mice as compared to 72.6 mm3 tumour, reduced by marketed IMQ cream with no significant difference (p > 0.05) at day 32 over 17-day period of treatment. IMQ-OLA cream followed the multiple mechanisms of cell death. IMQ-OLA cream warrants further in depth investigations for translating in to a clinically viable topical dermal product.

Design, development and characterization of ketorolac tromethamine polymeric nanosuspension.

Aim: At present, various ophthalmic formulations show low bioavailability. The rationale of present work was to design and develop stable ketorolac tromethamine nanosuspension with sustained effect and greater permeability for ocular drug delivery and increased ocular residence.Materials & methods:Formulations were designed by using central composite design, developed by combined nanoprecipitation and probe sonication method. Results & discussion: Nanosuspensions depicted the size range of the particles in between 199 and 441nm with slight reduction in crystallinity of drug. In vitro drug release revealed that higher % entrapment efficiency of drug in nanosuspension delays the drug release. Conclusion: Eudragit RL-100-based nanosuspension increases viscosity and avoids problems like drug loss from precorneal surface and rapid drainage through nasolacrimal areas.

Synergistic effect of polyethylene glycol and superdisintegrant on dissolution rate enhancement of simvastatin in pellet formulation

Slow dissolution is a major drawback for poorly water-soluble drugs when they are extruded-spheronized with microcrystalline cellulose (MCC). Therefore, the aim of the current study was to explore excipients to enhance the dissolution of simvastatin without compromising the extrudability and sphericity of pellets. Pellets containing simvastatin, MCC and polyethylene glycols (PEGs) or superdisintegrants were prepared by extrusion-spheronization and their micromeritics and mechanical properties, drug release and solid state of simvastatin were studied. All formulations produced pellets with reasonable size and sphericity. Generally, the inclusion of PEG and superdisintegrants decreased crushing strength and elastic modulus of pellets and increased the dissolution rate of simvastatin. A substantial increase in dissolution rate was observed when a combination of PEG and superdisintegrant was used due to the formation of more porous matrix, faster disintegration and remarkable reduction in drug crystallinity. It was interesting to note that the use of PEG and superdisintegrant had a synergistic effect on the dissolution enhancement of simvastatin in pellet formulation. The results of this study confirmed that a simple method of extrusion-spheronization can be employed to enhance the dissolution of simvastatin in multi particulates dosage form which can also be employed for other poorly water-soluble drugs.

MELOXICAM-PECTIN-β-CYCLODEXTRIN TERNARY COMPLEX BY KNEADING FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE

Objective: The objective of the present investigation was to improve the solubility and dissolution rate of poorly soluble drug meloxicam by its ternary inclusion complexation with natural polymers and beta-cyclodextrin (β-CD) by kneading.&#x0D; Methods: Equimolar physical mixture (1:1) was prepared by homogeneously kneading drug and β-CD using a solution of agar and pectin in water to get a paste, then paste was dried overnight to get inclusion complex. Inclusion complex was evaluated for drug content, the yield of the adsorption process, Fourier-transform infrared (FTIR), differential scanning calorimeter (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), dissolution, and stability studies.&#x0D; Results: The phase solubility diagrams exhibit AL showing a linear increase of drug solubility and indicating the formation of soluble complexes. The FTIR and DSC show compatibility between meloxicam and β-CD, while slight broadening in the peak with a reduction in intensity and early onset indicates the reduction in drug crystallinity which confirms in PXRD pattern. The SEM of binary, as well as ternary, showed no aggregation, and there was a gap between the particles also indicating good redispersibility. The dissolution rate of the drug from the kneaded ternary complex with pectin was significantly rapid compared with the pure drug. The maximum drug release was observed at 85.21±1.84% at the end of 60 min. The ternary complex was found stable after 3 months stability studies.&#x0D; Conclusion: The results indicated that ternary inclusion complexation with natural polymers and β-CD was most useful for enhancement of solubility and dissolution rate of a poorly soluble drug like meloxicam.

Preparation and Characterization of Glipizide Loaded Eudragit Microparticles

Background: Glipizide is an oral anti-diabetic drug used for the treatment of type II diabetes. Eudragit polymers are widely used for the sustained and targeted release of drugs. Encapsulated glipizide microparticles were developed using Oil-in-Water emulsion using Eudragit RS 100 -RL 100 in combination for sustained release of glipizide and its characterization for drug release and kinetics study. Objective: To develop glipizide loaded microparticles using combination of Eudragit RS 100 -RL 100 and to characterize for drug polymer interaction, surface morphology and drug release. Method: A 32 full factorial design was utilized for the preparation of microparticles and to understand the effect of input variable on output variables. The microparticles were characterized by Fourier Transform Infrared Spectroscopy for compatibility of drug and polymer, X-Ray diffractometer for crystallinity, Field emission scanning electron microscope for morphology study and in vitro drug release behaviour. Results: Percentage encapsulation efficiency and drug loading were obtained in the range of 45.5- 98.92% and 9.5-24.72% respectively. FTIR reveals the absence of chemical interaction between drug and polymer. XRD showed a reduction in crystallinity of drug. FE-SEM displayed spherical, nonaggregated porous microparticles. In vitro drug release studies showed sustained release of drug over a period of 12 h. Conclusion: The microparticles developed by this method were spherical and porous. The absence of drug-polymer interactions was confirmed by FTIR. Distribution of the drug within the polymers was confirmed by XRD. In vitro drug release studies showed sustained release of drug from encapsulated microparticles.

Formulation and Evaluation of Fast Dissolving Tablet Containing Vilazodone Nanocrystals for Solubility and Dissolution Enhancement Using Soluplus: In vitro-In vivo Study

Orally disintegrating tablets : formulation, preparation techniques and evaluationPriyanka Nagar, Kusum Singh, Iti Chauhan, Madhu Verma, Mohd Yasir,Azad Khan, Rajat Sharma, Nandini Gupta

Influence of Ispaghula and Zein Coating on Ibuprofen-Loaded Alginate Beads Prepared by Vibration Technology: Physicochemical Characterization and Release Studies.

The purpose behind the work was to fabricate alginate beads with better drug loading and extended drug release. Ispaghula was used to enhance the drug loading while zein was employed to extend the drug release. Ibuprofen was employed as a model drug in this study. Ibuprofen-loaded alginate beads with and without ispaghula were prepared using vibration technology and coated with zein. The beads prepared with alginate alone were shown to have loading and entrapment efficiencies of 35% and 70% w/w, respectively. Addition of ispaghula in alginate showed a significant increase (p < 0.05) in the drug loading (42% w/w) and entrapment efficiency (84% w/w). Fourier-transform infrared spectroscopy confirmed the presence of ispaghula and zein coating in the alginate beads as well as the ibuprofen loading. Scanning electron microscopy revealed better spherical geometry in the beads with ispaghula. The surface morphology of the uncoated beads was rough due to crystalline and surface drug. The zein coating has produced a smoother surface and particle adhesion. Differential scanning calorimetry has shown a reduction in drug crystallinity. Alginate beads extended the drug release for 4 h and the presence of zein extended the release for 6 h.

Peculiar effect of polyethylene glycol in comparison with triethyl citrate or diethyl phthalate on properties of ethyl cellulose microcapsules containing propranolol hydrochloride in process of emulsion-solvent evaporation

Plasticizers play a crucial role in various process of microencapsulation. In this study, the effect of incorporation of plasticizer in process of emulsion solvent evaporation was investigated on properties of ethyl cellulose (EC) microcapsules containing propranolol hydrochloride. The effect of plasticizer type and concentration were investigated on characteristics of microcapsules prepared from different viscosity grades of EC. Product yield, encapsulation efficiency, mean particle size, shape, surface characteristics, solid state of drug, and drug release profiles were evaluated. Product yield and encapsulation efficiency were not dependent on plasticizer type and concentration. However, encapsulation efficiency decreased with increase in EC viscosity grade in the most of the cases. The mean particle size was in the range of 724–797 μm and was not dependent on plasticizer type. Microcapsules formed in the presence of PEG had a very smooth surface with few pores. XRD and DSC studies revealed a reduction of drug crystallinity after microencapsulation especially in presence of PEG. The results showed that the presence of TEC and DEP with different concentrations had no marked effect on drug release from microcapsules containing different viscosity grades of EC. This was not the case when PEG was used, and despite its water solubility it reduced the drug release rate noticeably. The reduction in the drug release in the presence of PEG was concentration-dependent. The use of PEG as a plasticizer in process of emulsion solvent evaporation highly improved the EC microcapsule structure and retarded the drug release rate and therefore is recommended.

Flurbiprofen-loaded niosomes-in-gel system improves the ocular bioavailability of flurbiprofen in the aqueous humor

The present work aimed to prolong the contact time of flurbiprofen (FBP) in the ocular tissue to improve the drug anti-inflammatory activity. Different niosome systems were fabricated adopting thin-film hydration technique and using the nonionic surfactant Span 60. The morphology of the prepared niosomes was characterized by scanning electron microscopy (SEM). Physical characterization by differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy were conducted for the optimized formula (F5) that was selected on the basis of percent entrapment efficiency, vesicular size and total lipid content. F5 was formulated as 1% w/w Carpobol 934 gel. Pharmacokinetic parameters of FBP were investigated following ocular administration of F5-loaded gel system, F5 niosome dispersion or the corresponding FBP ocular drops to albino rabbits dispersion. Anti-inflamatory effect of F5-loaded carbopol gel was investigated by histopathological examination of the corneal tissue before and after the treatment of inflamed rabbit eye with the system. Results showed that cholesterol content, surfactant type. and total lipid contents had an apparent impact on the vesicle size of the formulated niosomes. Physical characterization revealed reduced drug crystallinity and incidence of interaction with other niosome contents. F5-loaded gel showed higher Cmax, area under the curve (AUC0–12), and thus higher ocular bioavailability than those of the corresponding FBP ocular solution. F5-loaded gel showed a promising rapid anti-inflammatory effect in the inflamed rabbit eye. These findings will eradicate the necessity for frequent ocular drug instillation and thus, improve patient compliance.

Design and Development of Fast Dissolving Tablet of Gliclazide

In the present study, Gliclazide is a second-generation sulfonyl urea derivative used to treat non-insulin dependent diabetes mellitus. The drug has been classified as class-II drug according to biopharmaceutical classification system having low solubility and high permeability. So, an attempt was made to enhance the solubility of gliclazide by solvent evaporation technique. A significant enhancement of gliclazide dissolution rate will be obtained using by using suitable techniques. In this PVP-k30, polyethylene glycol and soluplus were mixed with the drug in different ratios (1:1, 1:3) and prepare P1, P2, PE1, PE2, S1 and S2 solid dispersion batches. The optimized solid dispersions P1 were further kneaded with suitable proportions of super disintegrants such as; Cross carmellose and Sodium starch glycolate. Dissolution profile will show decrease amount of drug release at specified time. DSC as well as X-ray diffraction showed reduced drug crystallinity in SDs. Scanning electron microscopy and particle size analysis revealed significant decreased particle size of the drug in SDs. FT-IR spectroscopy demonstrated no detectable interactions between the drug and excipients. On that the P1 batch will be consider for eight different fast dissolving tablets Preparation. The prepared FDT’s were evaluated for various parameters like disintegration time, wetting time, drug content, in vitro drug release study etc. and shows the satisfactory result. The formulation of F-4 containing cross carmellose sodium (5%) showed better result in disintegration time 11 sec. and maximum in vitro drug release of 99.89% at the end of 40 minutes.

Formulation and development of embelin liquisolid systems using quality by design approach

The purpose of the present investigation was to improve dissolution properties of poorly water soluble herbal active ingredient, Embelin (EMB) by formulating liquisolid systems. The new mathematical model was employed for the preparation of the liquisolid systems. Drug loaded liquisolid systems were optimized by utilizing design of experiments (DoE) and principal component analysis (PCA) with carrier-coating ratio (X1) and drug concentration in liquid (X2) as factors. Angle of repose and percentage drug release in 30 min were selected as dependent variables. The liquisolid systems were prepared using Solutol® HS-15 in combination of Synperonic® PE/L61 in ratio of 1:1 as non-volatile liquid, Neusilin US2 as carrier and Aerosil 200 as coating material. The relationship between dependent and independent variables were further explicated through regression analysis and response surface plots. Prepared systems were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction studies. In-vitro dissolution results revealed significant enhancement in drug release properties from the formulations. Physicochemical characterization of liquisolid systems proposed reduction in drug crystallinity which might be ascribed for improvement in dissolution properties. Study demonstrated successful utilization of Solutol® HS-15 in combination of Synperonic® PE/L61 for dissolution enhancement of EMB.