Drug Dissolution Rate Research Articles

Stable and Fast-Dissolving Amorphous Drug Composites Preparation via Impregnation of Neusilin® UFL2

A promising approach to increase the aqueous solubility, hence the bioavailability, of poorly water-soluble drugs is to convert them into their amorphous state through impregnation into mesoporous silica. Unfortunately, mesoporous silica is not yet available in bulk quantities due to high manufacturing costs. In this work, feasibility of using a commercially available cost-effective mesoporous fine grade Neusilin® UFL2 to prepare amorphous drug composites of 2 model poorly soluble drugs, fenofibrate and itraconazole, is established. In contrast to fluidized-bed spray-impregnation, only mixing and drying steps are required. Complimentary assessment using X-ray powder diffraction, differential scanning calorimetry, and Raman spectroscopy confirmed drug within the composites to be amorphous at as high as 30% drug loading both after formation and after 3 months of storage at 40°C and 75% relative humidity. Amorphous drug recrystallization was completely suppressed due to the confinement effect due to the Neusilin®. The amorphous drug composites resulted in higher apparent solubility and faster dissolution rate of the model drugs as compared to their crystalline counterpart, confirmed by United States Pharmacopeia II dissolution and ultraviolet surface dissolution imaging. Overall, stable, high drug-loaded fast-dissolving amorphous drug composites preparation using Neusilin® UFL2 is demonstrated as a promising approach to enhance solubility of poorly soluble drugs.

Core-Shell Medicated Nanoparticles Prepared Using Coaxial Electrospray for Fast Dissolution of Paracetamol

Background The dissolution of insoluble drugs is one of the most intractable challenges in pharmaceutics, particularly for those used to rapidly bring down a fever or stop pain. Advanced technologies are frequently introduced into this field for developing nano drug delivery systems (DDS) for this purpose. Methods Coaxial electrospray is a popular advanced process for creating core-shell micro-/nano-structures. Here, a core-shell nano DDS was fabricated and characterised in detail for enhancing the fast dissolution of paracetamol. A surfactant solution (consisting of 0.5% w/v Triton X-100% and 10% w/v polyvinylpyrrolidone (PVP) K10 in ethanol) and a drug solution (composed of 5% w/v paracetamol and 10% w/v PVP K10 in ethanol) were exploited. Results Under the selected conditions (an applied voltage of 20 kV, a collecting distance of 15 cm, and a shell-to-core fluid flow rate ratio of 0.5/1.5 mL/h), uniform core-shell nanoparticles were stably and continuously fabricated. Owing to the secondary interactions between PVP and paracetamol, the particles were amorphous composites, as verified by the XRD patterns and attenuated total reflectance–FTIR spectra. The nanoparticles could release the loaded cargoes within one minute after they were placed into the dissolution media. Conclusion Core-shell medicated nanoparticles prepared using coaxial electrospray can be an alternative approach for improving the dissolution rate of insoluble drugs. Acknowledgements Supported by the National Natural Science Foundation of China (No. 51373101).

Formulation and Evaluation of Ciprofloxacin Solid Dispersion Controlled Release Floating Capsules for Solubility Improvement

Solid dispersions in water soluble carriers have attracted considerable interests as a mean of improving the dissolution rate and hence possibly bioavailability range of hydrophobic drugs. The poor solubility of ciprofloxacin leads to poor dissolution and hence variation in bioavailability. The purpose of present investigation was formulation and evaluation of controlled release floating capsule of ciprofloxacin with improved solubility and dissolution rate. In present study solid dispersion using various carriers like mannitol and lactose in different ratios were prepared by solvent evaporation method. The prepared solid dispersions were characterized for drug content, solubility and dissolution rate. The dissolution rate substantially improved for ciprofloxacin from its solid dispersions compared with pure drug. Dissolution rate increased with increase in carrier content. The dissolution rate was increased 3 folds with solid dispersions containing 1:4 of drug: lactose. The granules of ciprofloxacin solid dispersion containing 1:4 of drug: lactose ratio was prepared by wet granulation method using polymer such as ethyl cellulose and HPMC. The prepared granules were evaluated to preformulation studies such as angle of repose (18.41-24.22), bulk density, tapped density, compressibility index (11.31-12.75) and hausner’s ratio. All the parameters shows that the granules having good flow properties. These granules had converted into the capsule forms. Then the formulated capsules were taken to the evaluation studies such as weight variation, release study, buoyancy and floating duration (more than 6 hrs.). We can conclude that all the parameters were within the acceptable limits.

Effect of Ionic Liquids on the Separation of Sucrose Crystals from a Natural Product Using Crystallization Techniques

The present work aims to investigate the applicability of ionic liquids (ILs) for natural ingredient crystallization. First, the medicinal plant, namely Angelica gigas Nakai, was extracted using methanol (MeOH) as a solvent. Afterwards, ILs 1-butyl-3-methylimidazolium tetrafluoroborate (BMImBF4), 1-butyl-3-methylimidazolium hexafluorophosphate (BMImPF6), 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMImTFSI), 1-allyl-3-ethylim idazolium tetrafluoroborate (AEImBF4), and 1,3-diallyl imidazolium tetrafluoroborate (AAImBF4), in three ratios of 1:1, 1:2, and 1:3 (extraction solution/ILs (v/v)) were used as an anti-solvent to induce crystallization. Crystals were obtained within 8 h and were then identified to be pure crystals of sucrose through nuclear magnetic resonance (1H-NMR) analysis. Moreover, the single-crystal X-ray diffraction (SXD) analysis revealed all recovered crystals have an identical crystal structure and the morphology was monitored using a video microscope. With the application of BMImBF4 and BMImPF6, transformation of sucrose crystal morphology from an elongated hexagon shape to an elongated rectangular shape was observed with respect to the respective concentration increase. Here, all crystals precipitated from BMImBF4 and BMImPF6 were found to possess identical PXRD patterns. However, when BMImTFSI was employed, small rectangular crystals attached to the larger rectangular-shaped crystals due to secondary nucleation and shapeless amorphous forms were observed according to the alteration in the solution to ILs ratio. Accordingly, the ability of ILs as a relevant anti-solvent for the selective crystallization of a single compound from a natural product was assessed through the study. Furthermore, the applicability of ILs as crystal engineering solvents are expected to modify both the solid state and the crystal morphology of natural compounds, which can influence drug manufacturability, dissolution rate, and bioavailability.

SOLUBILITY AND DISSOLUTION ENHANCEMENT OF WATER INSOLUBLE DRUG BY USING DIFFERENT HYDROPHILLIC CARRIERS AND FORMULATED INTO TABLET DOSAGE FORM

Rosuvastatin calcium is a BCS class II drug (low solubility and high permeability), used as a lipid lowering agent by acting as HMG CoA reductase inhibitor and it is used for the management of hyperlipidemia. Increase in the solubility of the poorly water soluble drug is the most challenging aspect for various new chemical entities which leads to the unsatisfactory dissolution profile, consequently, the bioavailability. There are various techniques to enhance the solubility of the drug, such as particle size reduction, nanosuspension, use of surfactants, salt formation, pH modifier, solid dispersion etc. Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate and hence possibly bioavailability, of a range of hydrophobic drugs. Carriers are the major players in these formulations, e.g., hydroxypropylmethylcellulose, ethyl cellulose, methyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol etc. HPMC and EC is one of the most efficient polymers among all of these to work as a carrier for these drugs to enhance solubility. Four ratios of drug: carrier were prepared (1:1, 1:3, 1:5, 1:7) and 1:7 was the optimized ratio which shows a maximum release of the drug via dissolution profile. In the present work, Solid Dispersions were prepared by Kneading technique to enhance the solubility of Rosuvastatin Calcium. Solid dispersions were evaluated for Fourier transform infrared spectroscopy (FTIR), thermal analysis, dissolution studies, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and stability studies to confirm enhancement in solubility. The prepared solid dispersions are formulated into tablet dosage form and characterized by various parameters i.e. weight variation, hardness, friability, disintegration, and dissolution rate. The evaluated parameters of tablet dosage form show increase in solubility and dissolution rate of the pure drug. Keywords : Rosuvastatin Calcium, Carriers, HPMC, EC, Solid Dispersion Tablet

Carrier characteristics influence the kinetics of passive drug loading into lipid nanoemulsions

Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion-based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading. While the influence of the drug characteristics is mostly understood, the influence of the carrier characteristics remains unknown. The aim of this study was to examine how the lipid nanocarriers’ characteristics, i.e. the type of lipid, the lipid content and the particle size, influence the kinetics of passive loading. Fenofibrate was used as model drug and the loading progress was analyzed by UV spectroscopy. The saturation solubility in the nanocarrier particles, i.e. the lipid type, did not influence the passive loading rate constant. Low lipid content in the nanocarrier and a small nanocarrier particle size both increased passive loading speed. Both variations increase the diffusivity of the nanocarrier particles, which is the primary cause for fast loading at these conditions: The quicker the carrier particles diffuse, the higher is the speed of passive loading. The influence of the diffusivity of the lipid nanocarriers and the effect of drug dissolution rate were included in an overall mechanistic model developed for similar processes (A. Balakrishnan, B.D. Rege, G.L. Amidon, J.E. Polli, Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity, J. Pharm. Sci. 93 (2004) 2064–2075). The resulting mechanistic model gave a good estimate of the speed of passive loading in nanoemulsions. Whilst the drug’s characteristics – apart from drug surface area – are basically fixed, the lipid nanocarriers can be customized to improve passive loading speed, e.g. by using small nanocarrier particles. The knowledge of the loading mechanism now allows the use of passive loading for the straightforward, material-saving selection of suitable lipid drug nanocarriers.

RETRACTED: Development and characterisation of semi-crystalline composite granules: The effect of particle chemistry and the electrostatic charging

Abstract This study investigated the surface of semi-crystalline composite granules produced via a novel mechano-chemical process and assessed the effect of electrostatic charging. Ibuprofen (IBU), a model drug with low solubility and known associated processing challenges was loaded in composite granules to improve its processibility and dissolution rates. Synthetic amorphous mesoporous magnesium alumina metasilicate (MAS) was co-processed with hydrophilic HPMC polymer in the presence of polyethylene glycol 2000 (PEG) and deionised water. The solid state analyses conducted by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed the existence of semi-crystalline IBU in the complex composite structures. Dynamic vapour sorption (DVS) study showed the water sorption and desorption profiles of the manufactured composite granules as well as the effect of water on the solid-state stability of IBU in various formulations. Advanced surface analysis conducted via energy dispersive X-ray (EDS) revealed homogenous distribution of the drug/excipients on the surface of the granules while atomic force microscopy (AFM) complemented the findings. The electrostatic charge analysis showed variable charge property which is affected by the size of the particles/granules. As expected, the in vitro dissolution study showed about 5 fold increase in the release rates of IBU compared to that of the bulk drug. The mechanochemical processing has been demonstrated as an efficient technique to develop semi-crystalline composite granules with enhanced dissolution rates of water insoluble drugs.

Atomization of denatured whey proteins as a novel and simple way to improve oral drug delivery system properties

In the sphere of drug delivery, denatured whey protein (DWP) has in recent times gained press. However, to date, no scalable and affordable dosage form has been developed. The objective of our study was to evaluate the potential use of spray-dried DWP as a ready to use excipient for oral drug delivery. Therefore, solid state, FTIR spectra and wettability were studied. Dissolution, mucoadhesion and the effect on paracellular permeability were also evaluated. The spray-dried DWP particles were spherical with 4μm mean diameter. Further, relative to native WP, the spray-dried DWP particles bore reduced wettability, and their structure was characterized by the exposure of a high amount of free thiol and by the formation of intermolecular β-sheets. The DWP powders were mucoadhesive, enzymatic inhibitors, biocompatible and they induced the opening of tight junctions. Our study shows great potential for the use of spray-drying as a technique to modify the dissolution rate of drugs and enhance the oral bioavailability of molecules. That is, the use of spray drying as a single step ready to use DWP excipient.

LIQUISOLID COMPACTS: A PROMISING APPROACH FOR SOLUBILITY ENHANCEMENT

At present 40% of the drugs within the development pipelines, and approximately 60 % of the drugs coming directly from synthesis area unit poorly soluble. Â Solubility is one of the important parameter to obtain desired concentration of drug in systemic circulation. Liquisolid compacts technique is a new and promising approach to overcome this consequence and that can change the dissolution rate of water insoluble drugs and increase the bioavailability of the drugs. This technique is an efficient method for formulating water insoluble and water soluble drugs. This technique relies upon the admixture of drug loaded solutions with applicable carrier and coating materials. Liquisolid system is characterized by flow behaviour, wettability, powder bed hydrophilicity, saturation solubility, drug content, differential scanning calorimetry, Fourier transform infra-red spectroscopy, powder X-ray diffraction, scanning electron microscopy, in-vitro release and in-vivo evaluation. This review article explains the preparation, classification and application of liquisolid system. Key word: Liquisolid system, water insoluble drug, carrier material, coating materialÂ

SOLID DISPERSION TECHNOLOGY, A CONTEMPORARY OVERVIEW ON A WELL-ESTABLISHED TECHNIQUE

Solubility is a significant physicochemical parameter that affects the absorption, bioavailability and therapeutic effectiveness of any drug. Formulation development would fail if drug has a poor aqueous solubility. The low aqueous solubility of drug substances will lead to inadequate absorption and consequently, low bioavailability. Improvement of the aqueous solubility and dissolution rate of hydrophobic drugs remains one of the most difficult challenges in drug development process. Among various techniques used to improve poor aqueous solubility of drugs, solid dispersion technology has been extensively used in the literature and has become one of the well-established pharmaceutical procedures during formulation process. Although the technique seems to be “a part of the past”, literature tells us that it is still used and developed to suit current needs of pharmaceutical industry. This review article highlights recent advances in solid dispersion technology and its applications in contemporary pharmaceutical research. Peer Review History: Received 17 June 2017; Revised 25 June; Accepted 1 July, Available online 15 July 2017 Academic Editor: Dr. A.A. Mgbahurike, University of Port Harcourt, Nigeria, amaka_mgbahurike@yahoo.com 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. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Jennifer Audu-Peter, University of Jos, Nigeria, drambia44@gmail.com Dr. Mohammed Abdel-Wahab Sayed Abourehab, Umm Al-Qura University; Makkah Al-Mukarramah, Saudi Arabia, mohawahab2002@yahoo.com Similar Articles: FABRICATION AND CHARACTERIZATION OF EZETIMIBE SOLID DISPERSION FOR SOLUBILITY ENHANCEMENT DEVELOPMENT AND IN VITRO DISSOLUTION STUDY OF BINARY AND TERNARY SOLID DISPERSIONS OF ACECLOFENAC IN VITRO DISSOLUTION STUDY OF GLIMEPIRIDE FROM BINARY AND TERNARY SOLID DISPERSION FORMULATION This article has been cited by: Mahmoud A. Younis Helal F. Hetta Mohamed A. Y. Abdel-Malek Hassan Refat H. Ali Noha N. Atia Hesham M. Tawfeek. Combining acetyl salicylic acid and rofecoxib into novel oral tablets normalize platelet function with potential higher tolerability in patients with cardiovascular disorders . Journal of Drug Delivery Science and Technology Volume 59, October 2020, 101851.Pubmed

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions Hmix<−0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide.

Electrospun hypromellose-based hydrophilic composites for rapid dissolution of poorly water-soluble drug

Hypromellose (HPMC)-based hydrophilic composites (HCs) used for rapid dissolution of ferulic acid (FA) were investigated. Electrospun and casting HCs were prepared from a solution containing HPMC, FA, and polyethylene glycol. Ethanol was used as sheath fluid during coaxial processes, and the effects of its flow rates on the Taylor cone and straight fluid jet were investigated. The morphology, component state, hydrophilicity, and drug dissolution rate of the HCs were characterized. Results demonstrated that all HCs were amorphous materials, and their components were compatible. However, the dissolution rate of electrospun HCs was 10 times faster than that of casting HCs. The smaller the diameters of electrospun HCs were, the better their performances were. The mechanism of electrospun HCs was suggested. By utilizing modified coaxial electrospinning and combinations of drug carriers, new types of HPMC-based HCs can provide an alternative approach for the effective delivery of poorly water-soluble drugs.

Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome.

Complex regional pain syndrome type 1 (CRPS-I) is a disabling and frequently chronic condition. It involves the extremities and is a frequent consequence of distal tibia and radius fractures. The inflamed appearance of the affected CRPS-I limb suggests that local production of inflammatory mediators may be implicated in the ensuing etiology. A rodent tibia fracture model, characterized by inflammation, chronic unilateral hindlimb warmth, edema, protein extravasation, allodynia and hyperalgesia resembles the clinical features of patients with acute CRPS-I. N-palmitoylethanolamine (PEA), a member of the family of naturally-occurring N-acylethanolamines, is well-known for its ability to modulate inflammatory processes and regulate pain sensitivity. However, the large particle size and lipidic nature of PEA may limit its bioavailability and solubility when given orally. Micronized formulations are frequently used to enhance the dissolution rate of drug and reduce its variability of absorption when orally administered. The aim of this study was to assess the effects of a formulation of micronized and ultramicronized PEA (PEA-MPS), given orally in a mouse model of CRPS-I. CD-1 male mice were subjected to distal tibia fracture and divided into two groups: control and treated with PEA-MPS (PEA micronized 300 mg/kg and ultramicronized 600 mg/kg). Sensibility to pain was monitored in all mice throughout the course of the experiment. Twenty-eight days after tibia fracture induction animals were sacrificed and biochemical parameters evaluated. The PEA-MPS-treated group showed an improved healing process, fracture recovery and fibrosis score. PEA-MPS administration decreased mast cell density, nerve growth factor, matrix metalloproteinase 9 and cytokine expression. This treatment also reduced (poly-ADP)ribose polymerase activation, peroxynitrite formation and apoptosis. Our results suggest that PEA-MPS may be a new therapeutic strategy in the treatment of CRPS-I.

Etodolac Softgels: Feasibility Assessment and Considerations for Lipid-Based Formulations of a highly hydrophobic drug

Oral lipid-based formulations provide a significant opportunity to address the poor and variable gastrointestinal absorption associated with poorly water soluble drugs. It is useful to discuss how a formulation can strategize various options creatively to overcome some of the challenges posed by the softgel dosage form development of a highly hydrophobic drug with large dose. Etodolac (ETO) was formulated in different lipid vehicle according to Lipid Formulation Classification System (LFCS) to optimize the appropriate fill composition and was subjected to different tests for characterization. Water migration studies, rupture test and mechanical properties of softgels were also performed to investigate the effect of the formulation materials on the integrity, physical stability of the prepared capsules and on the dissolution characteristics of drug. Selected formulations were assessed for in vitro dissolution profile and rupture test for softgel before and after accelerated and shelf stability for 3 months. Results revealed a correlation between the composition of the softgel core fill liquid and drug dissolution parameters. Application of hydrophilic surfactants showed a remarkable enhancement in the dissolution rate of drug. The extent of migration of a solute between a fill and a shell depends on the hydrophilicity of the solute, composition of the shell formulation. Antioxidants should be added to formulations containing hydrophilic surfactants which composed of polyoxyethylene moiety. Nominated formula containing polyethylene glycol/poloxamar 407 showed a good and stable dissolution results after accelerated and shelf stability in addition to better mechanical results.

Evaluations of the Effect of Sodium Metabisulphite on the Stability and Dissolution Rates of Various Model Drugs from the Extended Release Polyethylene Oxide Matrices

PurposeThis study examines the effect of sodium metabisulphite (SMB) as an antioxidant on the stability and release of various model drugs, namely, propranolol HCl, theophylline and zonisamide from the polyethylene oxide (PEO) tablets. The antioxidant was used to minimise degradation and instability of the manufactured tablets when stored at 40 °C (55 ± 5% RH) over 8 weeks.MethodMultiple batches of tablets weighing 240 mg (50% w/w) with a ratio of 1:1 drug/polymer and 1% (w/w) sodium metabisulphite containing different model drugs and various molecular weights of PEO 750 and 303 were produced.ResultsThe results indicated that the use of sodium metabisulphite marginally assisted in reducing drug release and degradation via oxidation in propranolol HCl tablets containing both PEO 750 and 303. In the case of poorly and semi-soluble drugs (zonisamide and theophylline), the formulations with both PEO showed entirely superimposable phenomenon and different release profiles compared to control samples (matrices without SMB). DSC study demonstrated the modifications of the polymer due to degradation and observed the effect of SMB on the thermal degradation of the PEO matrices.ConclusionThe use of antioxidant has assisted in retaining the stability of the manufactured tablets with different model drugs especially those with the highly soluble drug that are susceptible to rapid degradation. This has been reflected by an extended release profile of various drugs used at various stages of the storage time up to 8 weeks.

A quality by design (QbD) twin—Screw extrusion wet granulation approach for processing water insoluble drugs

In this study, a Quality by Design (QbD) approach was used to identify the effect of formulation parameters in a twin screw wet extrusion granulation process for the manufacturing of ibuprofen (IBU) granules with increased dissolution rates. A fractional factorial Design of Experiment (DoE) was used to investigate the effect of the excipient composition, binder amount and liquid to solid (L/S) ratio (independent variables) on drug dissolution rates, median particle size diameter and specific surface area (dependent variables). The intra-granular addition of the binder in inorganic/polymer blends processed with ethanol as granulating liquids facilitated the formation of granules at various particle sizes. DoE regression analysis showed that all formulation parameters affect the dependent variables significantly. The enhanced dissolution rates were attributed not only to the IBU particle size reduction and adsorption in the porous inorganic network but also to the high specific surface area of the produced granules. Dynamic vapour sorption showed increased water absorption for granules with small particle size distribution and high specific surface area.

LIQUISOLID TECHNIQUE: A NOVEL APPROACH FOR DOSAGE FORM DESIGN

The liquisolid technique is a novel approach for delivery of drugs through the oral route. This technique is suitable for poorly soluble or water insoluble drugs, highly permeable drugs (BCS Class II drugs) and also for immediate or sustained release formulations. It is a novel "Powder Solution Technology" that involves absorption and adsorption efficiencies, making use of liquid medications, drug suspensions admixed with suitable carriers, coating materials and formulated into free flowing, dry looking, non-adherent and compressible powder forms. The design of liquisolid systems are mainly intended for enhancement of solubility, dissolution rate and bioavailability of poorly water-soluble and highly lipophilic drugs. Improvement in bioavailability may be due to increased surface area, increased aqueous solubility and increased the wettability of the drug. Liquisolid technique also has the potential to be optimized for the reduction of drug dissolution rate and thereby production of sustained release systems. Overall, liquisolid technique is a most promising and novel technique for enhancing the dissolution and bioavailability of poorly water soluble drugs and sustaining drug release from tablet matrices. The current review mainly focuses on theory and applicability of liquisolid compact technique towards solubility or bioavailability enhancement. Different carriers, solvents and coating materials employed are elucidated. Literature reports on the applicability of liquisolid compact techniques over a wide range of pharmaceutical formulations are also explicated.

Improved oral bioavailability of probucol by dry media-milling

The polymer/probucol co-milled mixtures were prepared to improve drug dissolution rate and oral bioavailability. Probucol, a BCS II drug, was co-milled together with Copovidone (Kollidon VA64, VA64), Soluplus, or MCC using the dry media-milling process with planetary ball-milling equipment. The properties of the milled mixtures including morphology, crystal form, vitro drug dissolution and in vivo oral bioavailability in rats were evaluated. Probucol existed as an amorphous in the matrix of the co-milled mixtures containing VA64, which helped to enhance drug dissolution. The ternary mixture composed of VA64, RH40, and probucol showed increased dissolution rates in both sink and non-sink conditions. It also had a higher oral bioavailability compared to the reference formulation. Dry-media milling of binary or ternary mixtures composed of drug, polymer and surfactant possibly have wide applications to improve dissolution rate and oral bioavailability of water-insoluble drugs.

Non-destructive prediction of enteric coating layer thickness and drug dissolution rate by near-infrared spectroscopy and X-ray computed tomography

The coating layer thickness of enteric-coated tablets is a key factor that determines the drug dissolution rate from the tablet. Near-infrared spectroscopy (NIRS) enables non-destructive and quick measurement of the coating layer thickness, and thus allows the investigation of the relation between enteric coating layer thickness and drug dissolution rate. Two marketed products of aspirin enteric-coated tablets were used in this study, and the correlation between the predicted coating layer thickness and the obtained drug dissolution rate was investigated. Our results showed correlation for one product; the drug dissolution rate decreased with the increase in enteric coating layer thickness, whereas, there was no correlation for the other product. Additional examination of the distribution of coating layer thickness by X-ray computed tomography (CT) showed homogenous distribution of coating layer thickness for the former product, whereas the latter product exhibited heterogeneous distribution within the tablet, as well as inconsistent trend in the thickness distribution between the tablets. It was suggested that this heterogeneity and inconsistent trend in layer thickness distribution contributed to the absence of correlation between the layer thickness of the face and side regions of the tablets, which resulted in the loss of correlation between the coating layer thickness and drug dissolution rate. Therefore, the predictability of drug dissolution rate from enteric-coated tablets depended on the homogeneity of the coating layer thickness. In addition, the importance of micro analysis, X-ray CT in this study, was suggested even if the macro analysis, NIRS in this study, are finally applied for the measurement.