Drug Dissolution Rate Research Articles

Impact of solidification on micromeritic properties and dissolution rate of self-nanoemulsifying delivery system loaded with docosahexaenoic acid

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of docosahexaenoic acid (DHA) is reported with the aim to achieve enhanced dissolution rate. The optimized composition of liquid SNEDDS (L-SNEDDS) formulation was Labrafil M1944 CS, 47% v/v Tween 80, 27% v/v Transcutol P, and 0.1% v/v DHA. L-SNEDDS were solidified using Syloid XDP 3150 as solid porous carrier. The droplet size, polydispersity index, zeta potential, percentage drug loading, and cloud point for L-SNEDDS were found to be 43.51 ± 1.36 nm, 0.186 ± 0.053, −19.20 ± 1.21 mV, 93.23 ± 1.71, and 88.60 ± 2.54 °C, respectively. Similarly, for solid SNEDDS (S-SNEDDS) the above parameters were found to be 57.32 ± 1.87 nm, 0.261 ± 0.043, −16.60 ± 2.18 mV, 91.23 ± 1.88, and 89.50 ± 1.18 °C, respectively. The formulations (L-SNEDDS, S-SNEDDS powder, and S-SNEDDS tablet) showed significant (p<.05) improvement in dissolution rate of drug in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) as compared to unprocessed DHA. In both the dissolution media, the dissolution rate was found more that 85% in 90 min. Absence of drug precipitation, phase separation, and turbidity during thermodynamic stability studies indicated that the developed SNEDDS were stable. Hence, it was concluded that SNEDDS have offered sufficient stability as well as dissolution rate of DHA.

IN VITRO-IN VIVO BIO-EQUIVALENCE CORRELATION STUDY OF METRONIDAZOLE, AND ITS BRANDS OF IMMEDIATE RELEASE TABLET UNDER BIO-WAIVER CONDITIONS

Objective: The aim of present study is to examine the in-vitro in-vivo correlation (IVIVC) of immediate release product. Metronidazole 500mg and its brands of immediate release dosage forms. Metronidazole is clearly classified into BCS class I, and could be evaluated under bio waiver conditions. Methods: The in vitro parameters employed were hardness, weight uniformity, friability, disintegration time, absolute drug content, dissolution rate (in 0.1 N Hydrochloric acid, phosphate buffer and acetate buffer at 37ºC), and dissolution efficiencies were also analyzed. The in-vitro dissolution study was performed on the brands, according to FDA,USP dissolution profile in three different PH (1.2), (4.5), and (6.8) at37ºC, using the USP apparatus II, then f1, f2 were determined for the time intervals of 10, 15, 30, 45 and 60 minutes, and dissolution efficiencies were calculated. MINITAB 14 statistical program used for in vitro in vivo correlation, level A was done for reference product. Results: A non linear relation was established which is typical for immediate release formulation, of class 1. There was significant relationship between in vitro and in vivo data of reference metronidazole product, Correlation and distribution of data with correlation coefficient (r=0.724, 0.837, 0.707), nonlinear relationship with p-value (&gt;0.05) =(0.167, 0.098, 0.182), there is no out lines, no lake of fits at P-Values=0.0040, 006, 0.026.Conclusion: Study concluded that there is no linear correlation between percent of drug released and percent of drug absorbed ,this may be due to uncontrollable gastric emptying rate for class one Metronidazole.&#x0D; Peer Review History: &#x0D; Received 2 January 2020; Revised 1 February; Accepted 3 March, Available online 15 March 2020&#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 4.5/10&#x0D; Average Peer review marks at publication stage: 7.0/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Hayriye Eda Şatana Kara&#x0D; Affiliation: Gazi University, Turkey&#x0D; E-mail: eda@gazi.edu.tr&#x0D; &#x0D; Name: Dr. Mohamed Ismail Nounou&#x0D; Affiliation: Appalachian College of Pharmacy, Oakwood, Virginia, USA&#x0D; E-mail: nounou@acp.edu&#x0D; Comments of reviewer(s): &#x0D; &#x0D; Similar Articles:&#x0D; IN VITRO-IN VIVO BIO-EQUIVALENCE CORRELATION STUDY OF ATENOLOL, AND ITS BRANDS OF IMMEDIATE RELEASE TABLET UNDER BIO-WAIVER CONDITIONS

Exploring the physical stability of three nimesulide–indomethacin co-amorphous systems from the perspective of molecular aggregates

Co-amorphization of drugs has been a promising approach to enhance the apparent solubility and dissolution rate of poorly-water soluble drugs. Nimesulide, a BCS Ⅱ drug, was combined with indomethacin to form three co-amorphous systems at molar ratios of 2:1, 1:1 and 1:2 via quench cooling. The aim of this research was mainly to probe the relationship between physical stability (long-term stability and temperature sensitivity) and intermolecular interaction modes among three co-amorphous systems. The calculated glass transition temperature by the Gordon-Taylor equation shows the presence of intermolecular interactions within co-amorphous systems. FTIR spectra further verify that there are hydrogen bonds and π–π stacking in intermolecular interactions. Specific atomic groups involved in the intermolecular hydrogen bonding were investigated using radial distribution function analysis based on molecular dynamic simulation. Gaussian calculation visually gives dominant molecular aggregate composed of multiple hydrogen bonding modes in co-amorphous systems and explains the stability difference of 1:2>1:1>2:1. Finally, powder dissolution profiles were conducted and the 1:2 system has the greatest dissolution advantage with six-fold improvement of dissolution rate compared with pure NMS.

Congruent Release of Drug and Polymer from Amorphous Solid Dispersions: Insights into the Role of Drug-Polymer Hydrogen Bonding, Surface Crystallization, and Glass Transition.

Drug loading is an important parameter known to impact the release rate of a poorly soluble drug from an amorphous solid dispersion (ASD). Recent studies have shown that small increases in drug loading can dramatically reduce the drug release rate from ASDs prepared with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA). However, the link between drug physicochemical properties and the drug loading where the release is abruptly compromised is not well understood. This study probes the role of different factors on the relative dissolution rates of drug and polymer from PVPVA-based ASDs as a function of drug loading: (1) the impact of drug-polymer hydrogen bonding interactions on the initial dissolution rate of ASDs, investigated using two structural analogues, indomethacin (IND) and indomethacin methyl ester (INDester), (2) the influence of surface drug crystallization, observed for INDester ASDs, and (3) by changing temperature, the impact of the "wet" glass transition temperature (Tg). Scanning electron microscopy (SEM), with or without energy dispersive X-ray (EDX) analysis, Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD) were utilized to study the solid-state phase behavior and/or drug enrichment on the partially dissolved ASD tablet surfaces. Nanoparticle tracking analysis (NTA) was utilized to study the solution-state phase behavior. It was found that, contrary to expectations, ASDs with drug-polymer hydrogen bonding exhibited poorer initial release at moderate drug loadings (15-25%) as compared to the non-hydrogen bonding analogue ASDs. Surface crystallization led to the deterioration of dissolution performance. Lastly, Tg relative to experimental temperatures also appeared to play a role in the observed dissolution behavior as a function of drug loading. These findings shed light on potential mechanisms governing ASD dissolution performance and will aid in the development of optimized ASD formulations with enhanced dissolution performance.

Formulation and In-vivo Studies of Clopidogrel by Self-nanoemulsifying Drug Delivery System

A self-nano emulsifying drug delivery system (SNEDDS) has been explored to improve poorly watersoluble drug clopidogrel’s solubility and dissolution rate. Different formulations were prepared using oil, surfactant, and co-surfactant in varying ratios. From the ternary phase diagram resultant formulations were investigated for clarity, phase separation, drug content, % transmittance, globule size, freeze-thaw, in vitro dissolution studies, particle size analysis, and zeta potential. Based on particle size, zeta potential and dissolution profile, and other studies, F6 was the best formulation of clopidogrel SNEDDS. The particle size of the optimized SNEDDS formulation was found to be 5.2 nm, and zeta potential was found to be -29 mV which complies with the requirement of the zeta potential for stability. The % release from optimized SNEDDS formulation F6 was highest (98.93%) and faster than other SNEDDS formulations and pure drug substance (32%), indicating the influence of droplet size on the drug dissolution rate. FTIR data revealed no physicochemical interaction between drug and excipients. In vivo bioavailability studies were carried out on the optimized formulation (F6), mean time to attain peak drug concentration (Tmax) was 0.5 ± 0.53 and 1.5 ± 0.72 minutes for the optimized and pure drug, respectively, while means maximum drug concentration (Cmax) was 6.77 ± 1.73 ng/mL and 2.10 ± 0.39 ng/mL respectively. AUC0-α and AUC0-t for the optimized formulation were significantly higher (p is less than0.05) 20.5 ± 2.48 ng.h/mL than the pure drug 6.34 ± 1.73 ng h/mL, respectively. Thus, the results indicate clopidogrel with SNEDDS formulation may be used to improve solubility and dissolution rate for the effective management of heart disease.

Methotrexate-loaded metal-organic frameworks on the basis of γ-cyclodextrin: Design, characterization, in vitro and in vivo investigation.

In this work, metal-organic frameworks on the basis of γ-cyclodextrin (γCD-MOF) were proposed as carriers for methotrexate (MTX) which is widely used as chemotherapy agent and immune system suppressant. The synthesized γCD-MOF was loaded with MTX by impregnation and co-crystallization. The obtained composites were characterized using powder X-ray diffraction, N2 adsorption/desorption, FTIR spectroscopy, solid-state 13C MAS CP/TOSS NMR and scanning electron microscopy. Pharmaceutically relevant properties of MTX alone and loaded in γCD-MOF were investigated in vitro and in vivo. The faster dissolution of MTX incorporated in γCD-MOF was demonstrated in blank buffers and biorelevant media (FaSSGF, FaSSIF) simulating the gastrointestinal fluids. Inclusion complex formation of MTX with γ-CD enhances the drug dissolution rate and, at the same time, slightly decreases the drug permeability through the lipophilic membrane. The in vivo experiments showed the improved pharmacokinetic parameters of MTX loaded in γCD-MOF.

Solubility enhancement of poorly aqueous soluble novel drug using natural gum as carriers

The current article is based on the concept to enhance the solubility and dissolution rate of a model drug, Rosuvastatin Calcium, which is BCS class-II drug with anti-hyperlipidemic potential. The reported bioavailability from oral route of drug is only 20%. So aim of current study is to improve the solubility and dissolution rate of a poorly water-soluble drug Rosuvastatin Calcium, by solid dispersion technique. Physical mixtures and solid dispersions were prepared using natural polymers A. Marmelos in different to drug to carrier ratios. Prepared formulations were characterized in solid state by FTIR analysis, powder X-ray diffraction, Scanning electron microscopy and in-vitro dissolution study. Solid state characterizations indicated the Rosuvastatin Calcium was present in amorphous form and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Rosuvastatin Calcium, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. The mixtures of solid dispersion and excipients were evaluated for pre-compression parameters. After then fast dissolving tablets were prepared by direct compression technique. The formulated tablets were evaluated by post compression parameters . In-vitro drug release performance of the developed formulations was investigated. Keywords: Solid Dispersion. Natural gums, Anti-lipidemic activity.

Evaluation of in situ gel forming system loaded with etoricoxib and herbal adjuvant nanoparticles against human colon cancer cell lines (HT-29)

The aim of the research work was to fabricate the nanosuspension of etoricoxib with polyherbal components (extract of ginger root and basil leaf) to enhance the solubility of API; furthermorein situ gel forming system for stomach specific drug delivery was prepared utilizing formulated nanosuspension as base. The objective of the present research is to enhance the solubility of poorly aqueous soluble drug by fabricating nanoparticles and improve their residence time within stomach by formulating in situ gel forming system. Tamarind seed polysaccharide as polymer, etoricoxib as drug, ethanolic extract of ginger (GE) and basil (BE), was used for preparation of nanoparticles.Solvent antisolvent precipitation method was used to prepare nanoparticles. The fabricated nanoparticles were evaluated for various parameters such as physical appearance, Scanning electron microscope, drug content, in-vitro drug release. For preparation of in-situ gel containing nanoparticles, tamarind seed polysaccharides, calcium carbonate and sodium alginate were used. The prepared formulations were evaluated for different characterization parameters such as,- pH, viscosity, floating behaviour, drug content, in-vitro drug release and in-vitro cytotoxic study. The in-situ gel containing nanoparticles were successfully prepared and evaluated. Firstly, the nanoparticles were evaluated for physical appearance, Scanning electron microscope, drug content, in-vitro drug release and found that the formulations were clear as well as homogenous, size of nanoparticles was evaluated in the range of 498nm to 587nm, the drug content of etoricoxib was found in the range of 71.38±0.01 (F5) to 79.45±0.01 (F6), the drug content of GE was found in the range of 69.25±0.05 (F4) to 74.25±0.02 (F1) and the drug content of BE was 69.48±0.09 (F1) to 75.59±0.08 (F6). The drug release was taken up to 12 h and found to be 99%. In-situ gel containing nanoparticles were also evaluated for different parameters such as pH, viscosity, floating behaviour, drug content, and in-vitro drug release. The pH of the prepared formulation was found to be in the range of 7.1±0.04 to 7.5±0.02. The viscosity of the prepared formulation was found in the range of 11.25±0.023 to 12.78 ±0.025. The lag time was found in the range of 11 to 20 sec and floating time was upto 24 h. The drug release was taken up to 8 h and found to be 99±0.2%. It can be concluded that etoricoxib with phytoconstituents (GE and BE) improved its potential to control the growth of human colon cancer cell line (HT-29) in in-vitro conditions. It was concluded from the findings that the in-situ gel containing nanoparticles of etoricoxib from solvent antisolvent method was successfully prepared and found that it has improved the solubility of the poorly soluble drug etoricoxib and dissolution rates.

Selection of In Vivo Predictive Dissolution Media Using Drug Substance and Physiological Properties

ABSTRACTThe rate and extent of drug dissolution in the gastrointestinal (GI) tract are highly dependent upon drug physicochemical properties and GI fluid properties. Biorelevant dissolution media (BDM), which aim to facilitate in vitro prediction of in vivo dissolution performance, have evolved with our understanding of GI physiology. However, BDM with a variety of properties and compositions are available, making the choice of dissolution medium challenging. In this tutorial, we describe a simple and quantitative methodology for selecting practical, yet physiologically relevant BDM representative of fasted humans for evaluating dissolution of immediate release formulations. Specifically, this methodology describes selection of pH, buffer species, and concentration and evaluates the importance of including bile salts and phospholipids in the BDM based upon drug substance log D, pKa, and intrinsic solubility. The methodology is based upon a mechanistic understanding of how three main factors affect dissolution, including (1) drug ionization at gastrointestinal pH, (2) alteration of surface pH by charged drug species, and (3) drug solubilization in mixed lipidic aggregates comprising bile salts and phospholipids. Assessment of this methodology through testing and comparison with literature reports showed that the recommendations correctly identified when a biorelevant buffer capacity or the addition of bile salts and phospholipids to the medium would appreciably change the drug dissolution profile. This methodology can enable informed decisions about when a time, complexity, and/or cost-saving buffer is expected to lead to physiologically meaningful in vitro dissolution testing, versus when a more complex buffer would be required.

IN VITRO-IN VIVO BIO-EQUIVALENCE CORRELATION STUDY OF ATENOLOL, AND ITS BRANDS OF IMMEDIATE RELEASE TABLET UNDER BIO-WAIVER CONDITIONS

The aim of present study is to examine the in-vitro-in-vivo correlation (IVIVC) of immediate release product. Atenolol 100mg and its brands of immediate release dosage forms. Atenolol is clearly classified into BCS class III, and could be evaluated under bio waiver conditions. The in vitro parameters employed were hardness, weight uniformity, friability, disintegration time, absolute drug content, dissolution rate (in 0.1 N Hydrochloric acid, phosphate buffer and acetate buffer at 37ºC), and dissolution efficiencies were also analyzed. The in-vitro dissolution study was performed on the brands, according to FDA,USP dissolution profile in three different PH (1.2),(4.5), and (6.8) at 37ºC, using the USP apparatus II, then f1, f2 were determined for the time intervals of 10, 15, 30, 45 and 60 minutes, and dissolution efficiencies were calculated. MINITAB 14 statistical program used for in vitro-in vivo correlation, level A was done for reference product. A non linear relation was established which is typical for immediate release formulation, of class III.&#x0D; Peer Review History: &#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 3.0/10&#x0D; Average Peer review marks at publication stage: 7.0/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Hayriye Eda Şatana Kara &#x0D; Affiliation: Gazi University, Turkey&#x0D; E-mail: eda@gazi.edu.tr&#x0D; &#x0D; Name: Dr. Nicola Micale &#x0D; Affiliation: University of Messina, Italy&#x0D; E-mail: nmicale@unime.it&#x0D; &#x0D; Comments of reviewer(s): &#x0D; &#x0D; Similar Articles:&#x0D; FAST DISSOLVING DRUG DELIVERY SYSTEMS: FORMULATION, PREPARATION TECHNIQUES AND EVALUATION &#x0D; FAST DISSOLVING TABLETS: A PROMISING APPROACH FOR DRUG DELIVERY &#x0D; DEVELOPMENT AND EVALUATION OF FAST DISSOLVING THIN FILMS OF ARIPIPRAZOLE &#x0D; TABLET GRANULATION: CURRENT SCENARIO AND RECENT ADVANCES &#x0D;

Role of wetting agents and disintegrants in development of danazol nanocrystalline tablets.

Poor wetting and/or particle aggregation are the shortcomings of the dried nanocrystalline suspensions, which subsequently might hinder the superior dissolution performance of the nano-crystalline suspensions. The objective of this study was to evaluate the effect of wetting agents and disintegrants on the dissolution performance of dried nanocrystals of an active pharmaceutical ingredient (API) with poor wetting property. Danazol, a BCS Class II compound with high LogP and low polar surface area, was chosen as a model compound for this study. Danazol nanocrystalline suspension was prepared by wet-media milling and converted into powder via spray granulation either with mannitol or microcrystalline cellulose as carriers at a drug: carrier ratio of 1:9 w/w. Danazol nanocrystalline suspension showed a superior dissolution performance compared to an un-milled danazol suspension. Dried danazol nanocrystals suffered from poor wetting leading to hindered dissolution performance i.e.~40% and~15% drug dissolution within 15min for the mannitol and microcrystalline cellulose-based granules, respectively. Addition of a lipophilic surfactant (i.e. docusate sodium) at a surfactant: drug ratio of 0.015: 1 w/w during granulation helped in retaining the superior drug dissolution rates i.e. more than 80% drug dissolution within 15min for mannitol-based granules by enhancing the wettability of dried danazol nanocrystals when compared to a hydrophilic surfactant (i.e. poloxamer 188) or disintegrant (i.e. sodium starch glycolate or croscarmellose sodium). The fast-dissolving mannitol-based granules containing danazol nanocrystals and docusate sodium were compressed into a tablet dosage form. The tablets containing danazol nanocrystals with docusate sodium showed a superior dissolution performance compared to a tablet containing un-milled danazol with docusate sodium.

Supersaturable organic-inorganic hybrid matrix based on well-ordered mesoporous silica to improve the bioavailability of water insoluble drugs

Mesoporous silica with uniform 2-D hexagonal pores has been newly employed as facile reservoir to impove the dissolution rate of water insoluble drugs. However, rapid drug release from mesoporous silica is usually accompanied by the generation of supersaturated solution, which leads to the drug precipitation and compromised absorption. To address this issue, a supersaturated ternary hybrid system was constructed in this study by utilizing inorganic mesoporous silica and organic precipitation inhibitor. Vinylprrolidone-vinylacetate copolymer (PVP VA64) with similar solubility parameter to model drug fenofibrate (FNB) was expected to well inhibit the precipitation. Mesoporous silica Santa Barbara amorphous-15 (SBA-15) was synthesized in acidic media and hybrid matrix was produced by hot melt extrusion technique. The results of in vitro supersaturation dissolution test obviously revealed that the presence of PVP VA64 could effectively sustain a higher apparent concentration. PVP VA64 was suggested to simultaneously reduce the rate of nucleation and crystal growth and subsequently maintain a metastable supersaturated state. The absorption of FNB delivered by the organic-inorganic hybrid matrix was remarkably enhanced in beagle dogs, and its AUC value was 1.92-fold higher than that of FNB loaded mesoporous silica without PVP VA 64. In conclusion, the supersaturated organic-inorganic hybrid matrix can serve as a modular strategy to enhance the oral availability of water insoluble drugs.

Solid Dispersion: Recapitulation

The approach to improve dissolution rate of hydrophobic drug and enhance the bioavailability, solid dispersion is one of the promising approaches in which dispersion of one or more drug substances (API) in a hydrophilic carrier at solid state is used. Among all newly discovered chemical entities about 40% drugs are lipophilic and hence fail to reach the market due to poor water solubility. The review highlights the timeline of solid dispersion approach and summarizes the development over the years and its potentiality in the future.

Crystallographic and Energetic Insights into Reduced Dissolution and Physical Stability of a Drug-Surfactant Salt: The Case of Norfloxacin Lauryl Sulfate.

A commonly used pharmaceutical surfactant, sodium lauryl sulfate (SLS), has been reported to reduce the dissolution rate of drugs due to the formation of a less soluble drug-lauryl sulfate salt. In this study, we provide direct crystallographic evidence of the formation of salt between SLS and norfloxacin (NOR), [NORH+][LS-]·1.5 H2O. The available crystal structure also enables the use of the energy framework to gain an understanding of the structure-property relationship. Results show that the hydrophobic methyl groups in SLS dominate the surfaces of the [NORH+][LS-]·1.5 H2O crystals, resulting in the increased hydrophobicity and reduced wettability by aqueous media. Moreover, an analysis of molecular environments and energy calculations of water molecules provides insight into the stability of [NORH+][LS-]·1.5 H2O with variations in the relative humidity and temperature. In summary, important pharmaceutical properties, such as solubility, dissolution, and thermal stability, of the drug-surfactant salt [NORH+][LS-]·1.5 H2O have been characterized and understood based on crystallographic and energetic analyses of the crystal structure.

Combined Use of Polymers and Porous Materials to Enhance Cinnarizine Dissolution

Background: Loading of poorly water-soluble drugs on the porous materials has attracted great interest as an effective approach for enhancement of dissolution rate of drugs. The Aerosil (Ae) with porous structure is expected to facilitate the dissolution of drugs which is generally associated with precipitation. Thus, the purpose of this investigation was thus to develop a formulation which combines a precipitation inhibitor and a poorly soluble drug loaded Ae. Methods: A poorly water-soluble drug, Cinnarizine (CNZ) was used as a model, and Eudragit L100 (Eu) was used as a precipitation inhibitor. Formulations were produced by solvent evaporation and characterized by FT-IR and differential scanning calorimetry (DSC). Dissolution experiments were carried out in phosphate buffer (pH 6.8) under non-sink conditions. Results: DSC thermograms revealed that no crystalline structure of CNZ was present in CNZ-loaded Ae formulations and no long-range order was arranged upon loading of CNZ into Ae. In dissolution test, the CNZ-loaded Ae physically blended with Eu achieved a remarkedly higher CNZ concentration over the plain CNZ and over the CNZ-Eu co-loaded Ae. The dissolution rate of CNZ from the CNZ-loaded Ae was enhanced with increasing Ae amount and the dissolution was maximum when the ratio of CNZ: Ae was 1:10 CNZ: Ae. In addition, the precipitation inhibition was increased when the amount of Eu was high. Conclusion: The results of this work revealed that the dissolution behaviour of CNZ-loaded Ae is enhanced by physically blending of Eu as a suitable precipitation inhibitor.

The Improved Cargo Loading and Physical Stability of Ibuprofen Orodispersible Film: Molecular Mechanism of Ion-Pair Complexes on Drug-Polymer Miscibility

High drug cargo loading in polymer and physical stability was essential for the development of orodispersible films (ODFs) because of the small amount of excipients used in a thin film. The present study aimed to investigate the mechanism of ion-pair strategy in improving drug cargo loading and physical stability of drug in ODFs. The results showed that the ion pair, especially ibuprofen-ethanolamine, improved the drug solubility in polymer up to 60% (w/w) and physical stability by 30% than the pure ibuprofen film. In addition, drug dissolution rate was increased over 2 times. The high drug cargo loading, physical stability and drug dissolution rate was derived from the improved the drug-polymer miscibility introduced by the formation of ion-pair complex. Investigations from the standpoint of physicochemical properties, intermolecular interaction, and polymer mobility indicated the modulation mechanism of ion-pair complexes in the ODFs at molecular level. The amino group and −OH of counter ion exhibited strong hydrogen bond forming ability, which increased the bilateral interaction with both drug and polymer, delayed the onset temperature of sublimation and decreased the polymer mobility. Therefore, ion-pair technology is a promising strategy for high drug loading ODFs in improving the drug-excipient miscibility and stability.

Improving the Dissolution of Triclabendazole from Stable Crystalline Solid Dispersions Formulated for Oral Delivery.

Triclabendazole belongs to the class II/IV of the Biopharmaceuticals Classification System, and its low aqueous solubility represents a major drawback during the development of effective dosage forms. Therefore, the goal of this study was to elucidate whether polymeric solid dispersions would represent a suitable approach to overcome such disadvantage. Due to the lack of information on triclabendazole release, four different dissolution media were evaluated to analyze drug dissolution rate. The polymeric solid dispersions were characterized by X-ray diffraction and Fourier transform infrared spectroscopy. The selected final formulations were further stored for 24 months, and their physical stability was evaluated by means of X-ray diffraction and drug dissolution assays. Drug solubility studies indicated that poloxamer 407 (P407) solubilized a higher amount of drug than polyethylene glycol 6000. Drug-to-carrier ratio, nature of the selected carriers, and the type of dissolution media were important factors for increasing dissolution. By infrared spectroscopy, there were no specific interactions between the drug and polymers. The physicochemical characterization of the systems showed a detectable evidence of drug amorphization by increasing the carrier ratio. Micromeritic studies indicated that raw triclabendazole, physical mixtures, and reference formulation showed poor flow properties, in contrast to the triclabendazole:P407 solid dispersion sample. Both the crystalline properties and dissolution rate of selected samples were very similar after 24 months at room temperature. Thus, considering physical stability and dissolution studies, the development of the solid dispersion is a very suitable methodology to improve triclabendazole dissolution and, potentially, its biopharmaceutical performance.

Improvement of Solubility and Dissolution Rate of Simvastatin by Solid Dispersion Technique

The aim of present work is to enhance the solubility and bioavailability of Simvastatin by solid dispersion technique and characterize the same. Preliminary solubility studies were conducted to check the solubility in different polymers. Based on the results 20 formulations prepared by solvent evaporation method with varying ratios of Kleptose HPB, Soluplus, Kolliwax GMS II, Kolliphor P188 and PVPK-30. All the formulations were analyzed for solubility, percentage yield, drug content and in vitro drug release. The formulation SD20 with enhanced solubility of 20.05 ± 0.02μg/mL in Kolliwax GMS II, percentage yield of 99.13% and dissolution rate of 99.2 ± 2.3% within 90 min is chosen as optimized formulation. The formulation is further Characterized for Drug excipient interaction by FTIR, PXRD and SEM studies. The stability studies for 6 months indicated no significant changes in drug content or drug dissolution rate. Hence, improve dissolution characteristics of Simvastatin achieved by increasing its release and solubility through solid dispersion technique.

DEVELOPMENT AND EVALUATION OF LAMOTRIGINE SOYA LECITHIN SOLID DISPERSION: IN VITRO AND PHARMACODYNAMIC INVESTIGATION

Objective: Epilepsy is a common neurodegenerative disorder characterized by spontaneous and repeated attacks of convulsions. It requires immediate pharmacotherapy to prevent its progression to status epilepticus. However, most of the anticonvulsant drugs are poorly water-soluble and demonstrate the delayed onset of action. Thus there is a need to improve its solubility for the better pharmaceutical profile. The objective of the present investigation was to enhance the solubility of lamotrigine incorporating soya lecithin as a phospholipid carrier by solid dispersion technique&#x0D; Methods: Solid dispersions of lamotrigine were prepared with soya lecithin by the solvent method. The effect of concentration of phospholipid and solvents on aqueous solubility and dissolution profile of lamotrigine was analyzed.&#x0D; Results: Ethanol increased lamotrigine solubility with soya lecithin in ratio 5:1. X-ray diffraction and scanning electron micrograph indicated a smaller crystallite size of lamotrigine with fairly uniform size distribution in the lamotrigine-soya lecithin solid dispersion. The resultant solid dispersion also significantly delayed the onset of clonic convulsion (875.8 s) as compared to control (85.5 s) and offered complete protection (100%) against the pentylenetetrazole induced seizures in the rat as compared to control (33.33%). Also, solid dispersion with maximum drug content (77.68%) and dissolution rate (91.40%) was formulated as an orodispersible tablet and characterized for its pharmaceutical properties.&#x0D; Conclusion: It can be concluded that the solid dispersion of lamotrigine incorporated with soya lecithin demonstrated enhanced solubility and dissolution rate may have potential clinical application.

Synthesis and characterization of mesoporous SBA-15 and SBA-16 as carriers to improve albendazole dissolution rate

Albendazole (ABZ, anti-parasitic active pharmaceutical ingredient) is a crystalline low water-soluble drug, thus the dissolution rate in gastrointestinal fluids is limited. Consequently, the improvement of the water solubility and dissolution rate of ABZ implies a great challenge for a more efficient treatment of hydatidosis. In this context, SBA-15 and SBA-16 ordered mesoporous silica materials were synthetized and loaded with ABZ. X-ray diffraction, FT-IR spectroscopy, nitrogen physisorption manometry, particle size distribution and scanning electronic microscopy were used to characterize unloaded and loaded materials (ABZ/SBA-15 and ABZ/SBA-16). The loaded ABZ amount in the carriers was estimated by elemental analysis. For the loaded materials, the drug solubility and release profile were evaluated. In addition, mathematical models were compared to explain the dissolution kinetics of ABZ from mesoporous solids. ABZ was successfully loaded into the mesopores. The amorphous state of the adsorbed ABZ was confirmed by differential scanning calorimetry that resulted in a notable increment in the dissolution rate compared to crystalline ABZ. Drug release behaviors were well simulated by the Weibull model for ABZ/SBA-15 and by the Gompertz function for pure ABZ and ABZ/SBA-16. The SBA-15 carrier exhibited the highest drug loading and dissolution rate becoming a promising material to improve ABZ bioavailability.