Bioavailability Enhancement Research Articles

Development of posaconazole nanosuspension for bioavailability enhancement: Formulation optimization, in vitro characterization, and pharmacokinetic study

Development of posaconazole nanosuspension for bioavailability enhancement: Formulation optimization, in vitro characterization, and pharmacokinetic study

Formulation and Evaluation of Multiple Emulation of Diclofenac Sodium

Abstract: Multiple emulsion is novel approach of drug delivery system for enhancement of bioavailability and pharmacological activity. It is important to prevent the problem of oral drugdelivery system and they are stabilized by using of combination of hydrophilic and lipophilic surfactant. The specific ratio of surfactant concentration is responsible for maintaining the stability of multiple emulsions, the importance of this study was to prepare multiple emulsion of Diclofenac sodium by using two step emulsification process, by using the non-ionic surfactant units. In multiple emulsion, the stability of multiple emulsion was evaluated, percent entrapment efficiency as well as in vitro studies are conducted. The objective of this study was to prepare multiple emulsion of Valsartan by two step emulsification using different nonionic surfactants, Tweens & Spans, and evaluate for stability,percentage drug entrapment, in vitro drug release.

Advancement in Solubilization Approaches: A Step towards Bioavailability Enhancement of Poorly Soluble Drugs.

A drug's aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70-90% of drug candidates in the development stage are poorly soluble, which results in low bioavailability, diminished therapeutic effects, and dosage escalation. Because of this, solubility must be taken into consideration when developing and fabricating pharmaceutical products. To date, a number of approaches have been investigated to address the problem of poor solubility. This review article attempts to summarize several conventional methods utilized to increase the solubility of poorly soluble drugs. These methods include the principles of physical and chemical approaches such as particle size reduction, solid dispersion, supercritical fluid technology, cryogenic technology, inclusion complex formation techniques, and floating granules. It includes structural modification (i.e., prodrug, salt formation, co-crystallization, use of co-solvents, hydrotrophy, polymorphs, amorphous solid dispersions, and pH variation). Various nanotechnological approaches such as liposomes, nanoparticles, dendrimers, micelles, metal organic frameworks, nanogels, nanoemulsions, nanosuspension, carbon nanotubes, and so forth have also been widely investigated for solubility enhancement. All these approaches have brought forward the enhancement of the bioavailability of orally administered drugs by improving the solubility of poorly water-soluble drugs. However, the solubility issues have not been completely resolved, owing to several challenges associated with current approaches, such as reproducibility in large scale production. Considering that there is no universal approach for solving solubility issues, more research is needed to simplify the existing technologies, which could increase the number of commercially available products employing these techniques.

Preparation of Melatonin Nanoparticles and their Enhancement of Lungs Bioavailability in the Treatment of Lungs Cancer

Niyaz Ahmad1,2, Mohammed Saifuddin Khalid3, Ayman Makki Al Ramadhan1, Mohammed Riyad Al Hammad1, Mohd Faiyaz Khan4, Ziyad Saeed Almalki4, Faisal K Alkholifi5, Zabih Ullah6, Mohd Ibrahim Khan7 and Nazia Khan8 Author informationArticle notesCopyright and License information 1Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, SAUDI ARABIA 2Department of Pharmaceutics, School

A Systematic Review of Piperine as a Bioavailability Enhancer

Drug oral absorption is a crucial concern, particularly when the medication is costly, poorly bioavailable, and administered for extended periods of time. Chemical substances known as "bioenhancers" are those that, when combined with pharmaceuticals, increase their bioavailability without having a synergistic impact on the drug itself. Toxicity, expense, poor bioavailability, and long-term medication administration all contribute to the need for bioenhancers, which aid in solving the majority of these issues. Piperine, also known as 1-peperoyl piperidine, is an aromatic alkaloid produced by the Piper species. Piperine alters the lipid milieu and membrane dynamics at the site of absorption to improve permeability. The molecular nature of piperine makes it appropriate for inhibiting enzymes. By blocking several metabolising enzymes, it increases the bioavailability of many medications, including carbamazepine, curcumin, ciprofloxacin, ampicillin, metronidazole, oxytetracycline, and many more. As a result, piperine, a potent inhibitor of medication metabolism, effectively increases absorption. The mechanism, metabolic inhibition, influence of structural alterations on activity, and medications that are bioenhanced by piperine are all explored in the review that follows. It offers insight into the use of piperine as a useful bioenhancer and the advantages of a bioenhanced drug formulation over one without one. Bioavailability enhancers are typically plant-based molecules that support the biological activity, bioavailability, or uptake of drugs in combination therapy. This review article finishes with discussing piperine's capacity to increase bioavailability.
 Keywords: Bioenhancers, Piperine, Oral absorption, Alkaloid.

Encapsulation of morin in lipid core/PLGA shell nanoparticles significantly enhances its anti-inflammatory activity and oral bioavailability

Morin (3,5,7,2′,4′-pentahydroxyflavone; MR) is a bioactive plant polyphenol whose therapeutic efficacy is hindered by its poor biopharmaceutical properties. The purpose of this study was to develop a nanoparticle (NP) formulation to enhance the bioactivity and oral bioavailability of MR. The nanoprecipitation techniquewas employed to encapsulate MR in lipid-cored poly(lactide-co-glycolide) (PLGA) NPs. The optimal NPs were about 200 nm in size with an almost neutral surface charge and a loading efficiency of 82%. The NPs exhibited sustained release of MR within 24 h. In vitro antioxidant assays showed that MR encapsulation did not affect its antioxidant activity. On the other hand, anti-inflammatory assays in lipopolysaccharide-stimulated macrophages revealed a superior anti-inflammatory activity of MR NPs compared to free MR. Furthermore, oral administration of MR NPs to mice at a single dose of 20 mg/kg MR achieved a 5.6-fold enhancement in bioavailability and a prolongation of plasma half-life from 0.13 to 0.98 h. The results of this study present a promising NP formulation for MR which can enhance its oral bioavailability and bioactivity for the treatment of different diseases such as inflammation.

Development and in Vitro/In Vivo Evaluation of Itopride Hydrochloride Expanding Tablets

PurposeGastroretentive drug delivery systems (GRDDS) have attracted interest for enhancement of absorption and bioavailability of some drugs. Itopride hydrochloride (ITOP) is a drug used for treatment of gastroesophageal reflux and other gastric motility disorders, but is characterized by narrow absorption window and short in vivo half-life. Therefore, it is expected that its formulation in expanding gastroretentive tablets would increase its gastric residence, thus leading to decreased frequency of administration and increased patient compliance.MethodsThe direct compression method was used for formulation of tablets. Four different hydrophilic polymers (xanthan gum, sodium alginate, gellan gum, pectin) were screened separately with Avicel 102 and PVP k30 as excipients. The effect of different factors (polymer type and amount, and excipient amount) on the tablet properties such as hardness, friability, thickness, diameter, weight variation, swelling, and in vitro drug dissolution was studied. In addition, swelling test, accelerated stability test, and in vivo study were performed on the optimized formulation.ResultsTablets prepared using xanthan gum exhibited favorable properties compared to tablets prepared using the other gums, however increasing the polymer amount led to increased tablet friability. The selected formulation exhibited obvious expansion reaching 17.45 mm and lasting for 24 h, coupled with a sustained release behavior. X-ray scans in human volunteers suggested the residence of the tablet in the stomach for a period of 6 h in fed state.ConclusionSuccessful preparation of directly compressible ITOP expanding tablets was achieved in this study, which is expected to result in better therapeutic outcome in gastroesophageal reflux.

Molecular Interactions between APIs and Enteric Polymeric Excipients in Solid Dispersion: Insights from Molecular Simulations and Experiments.

Solid dispersion of poorly soluble APIs is known to be a promising strategy to improve dissolution and oral bioavailability. To facilitate the development and commercialization of a successful solid dispersion formulation, understanding of intermolecular interactions between APIs and polymeric carriers is essential. In this work, first, we assessed the molecular interactions between various delayed-release APIs and polymeric excipients using molecular dynamics (MD) simulations, and then we formulated API solid dispersions using a hot melt extrusion (HME) technique. To assess the potential API-polymer pairs, three quantities were evaluated: (a) interaction energy between API and polymer [electrostatic (Ecoul), Lenard-Jones (ELJ), and total (Etotal)], (b) energy ratio (API-polymer/API-API), and (c) hydrogen bonding between API and polymer. The Etotal quantities corresponding to the best pairs: NPX-Eudragit L100, NaDLO-HPMC(P), DMF-HPMC(AS) and OPZ-HPMC(AS) were -143.38, -348.04, -110.42, and -269.43 kJ/mol, respectively. Using a HME experimental technique, few API-polymer pairs were successfully extruded. These extruded solid forms did not release APIs in a simulated gastric fluid (SGF) pH 1.2 environment but released them in a simulated intestinal fluid (SIF) pH 6.8 environment. The study demonstrates the compatibility between APIs and excipients, and finally suggests a potential polymeric excipient for each delayed-release API, which could facilitate the development of the solid dispersion of poorly soluble APIs for dissolution and bioavailability enhancement.

Enhanced biopharmaceutical performance of brick dust molecule nilotinib via stabilized amorphous nanosuspension using a facile acid-base neutralization approach.

"Brick dust" compounds have high lattice energy as manifested by the poor aqueous solubility and suboptimal bioavailability. Nilotinib being a weakly basic brick dust molecule exhibits erratic and limited absorption during gastrointestinal transit, attributed to pre-absorptive factors like pH-dependent solubility, poor dissolution kinetics, and post-absorptive factors including P-gp-mediated drug efflux. In our study, these problems are addressed holistically by the successful fabrication of amorphous nanosuspension by an acid-base neutralization approach. The nanosuspension was obtained via rapid precipitation of nilotinib in an amorphous form and the generated in situ sodium chloride salt assisted in stabilizing the drug-loaded nanosuspension in a cage of salt and micellar stabilizer. Soluplus® and hypromellose acetate succinate (HPMCAS) were employed as a novel combination of stabilizers. Systematic optimization was carried out by employing the I-optimal method using Design Expert®software with a concentration of HPMCAS and Soluplus®as independent variables and evaluating them for responses viz particle size, polydispersity index (PDI), and zeta potential. The resultant nanosuspension showed a mean particle size of 130.5 ± 1.22nm with a PDI value of 0.27 ± 0.01, and a zeta potential of - 5.21 ± 0.91mV. The nanosuspension was further characterized for morphology, dissolution, and in vivo pharmacokinetics study. X-ray powder diffraction study of the nano-formulation displayed a halo pattern revealing the amorphous form. Stability studies showed that the nanosuspension remained stable at 40°C ± 2°C and 75% RH ± 5% RH for a period of three months. In vitro drug release and solubility study showed threefold and 36-fold enhancement in dissolution and solubility of the nanosuspension. Furthermore, an in vivo pharmacokinetic study in Sprague-Dawley rats following oral administration displayed a 1.46-fold enhancement in the relative bioavailability of the nanosuspension in contrast to neat nilotinib.

Development of Diphenyl carbonate-Crosslinked Cyclodextrin Based Nanosponges for Oral Delivery of Baricitinib: Formulation, Characterization and Pharmacokinetic Studies.

The aim of the present investigation is to prepare baricitinib (BAR)-loaded diphenyl carbonate (DPC) β-cyclodextrin (βCD) based nanosponges (NSs) to improve the oral bioavailability. BAR-loaded DPC-crosslinked βCD NSs (B-DCNs) were prepared prepared by varying the molar ratio of βCD: DPC (1:1.5 to 1:6). The developed B-DCNs loaded with BAR were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), % yield and percent entrapment efficiency (%EE). Based on the above evaluations, BAR-loaded DPC βCD NSs (B-CDN3) was optimized with mean size (345.8±4.7 nm), PDI (0.335±0.005), Yield (91.46±7.4%) and EE (79.1±1.6%). The optimized NSs (B-CDN3) was further confirmed by SEM, spectral analysis, BET analysis, in vitro release and pharmacokinetic studies. The optimized NSs (B-CDN3) showed 2.13 times enhancement in bioavailability in comparison to pure BAR suspension. It could be anticipated that NSs loaded with BAR as a promising tool for release and bioavailability for the treatment of rheumatic arthritis and Covid-19.

Quality-by-design based fabrication of febuxostat-loaded nanoemulsion: Statistical optimization, characterizations, permeability, and bioavailability studies

The present work deals with QbD-based development of FEB-loaded nanoemulsion (FEB-NE) in order to enhance bioavailability and permeability. In the beginning, the risk assessment was performed on different experimental variables using the Ishikawa diagram followed by FMEA study in order to find critical process parameter (CPP) and critical material attributes (CMAs). To build quality in nanoemulsion, the quality target product profiles (QTPP) and critical quality attributes (CQAs) were determined. The different batches of FEB-NE were produced by the microemulsification-probe sonication method. Effect of varying levels of independent variables such as oil concentration (X1), Smix concentration (X3), and amplitude (X3) on responses such as globule size (Y1), zeta potential (Y2), and entrapment efficiency (Y3) were studied using Box-Behnken design (BDD). FEB-NE formulation was optimized using a graphical and numerical method. The optimized formulation concentrations and their responses (CQAs) were located as design space in an overlay plot. The spherical shapes of globules were visualized by surface morphology using AFM and TEM. In vitro dissolution study showed 93.32% drug release from the optimized FEB-NE formulation. The drug release mechanism followed by the formulation was the Higuchi-matrix kinetics with a regression coefficient of 0.9236 (R2). FEB-NE showed enhanced permeability using PAMPA (artificial non-cell membrane) and everted gut sac model method. The developed optimized FEB-NE exhibited the enhancement of bioavailability by 2.48 fold as compared to FEB-suspension using Wistar rats suggesting improvement of solubility of a lipophilic drug. The optimized batch remained stable for 90 days at 4 °C and 25 °C. Thus, QbD-based development of FEB-NE can be useful for a better perspective on a commercial scale.

Nano formulation approaches for curcumin delivery- a review

Curcumin is a polyphenol molecule derived from Curcuma longa Linn's rhizomes. Curcumin appears to have been the target of substantial research, with cancer, viral, fungal infections, bacterial, arthritis, antioxidant, anti-inflammatory, allergies, Alzheimer's disease, and other chronic diseases and disorders all being explored. Curcumin has undesirable features such as inadequate intake and low aqueous solubility. To resolve these challenges, research has taken numerous attempts to improve its absorption, solubility, and bioavailability. Nanotechnology plays a critical role in the creation of nanostructured devices, nanomedicines, targeted therapy, and nanocarriers. Curcumin nano formulation has alleviated some of the major disadvantages of curcumin-based medication delivery. The emphasis of the study is on nano-based techniques to address therapeutic activity, efficacy, bioavailability, and solubility. Curcumin was localized to a certain cellular and molecular level by combining nano-curcumin with a specific molecule to enhance activity at the target site. A detailed description of solubility and bioavailability enhancement technique using protein carriers, solid dispersions, nanofiber, carbon dots, liposomes, and polymer carrier drug delivery systems is provided in this review.

Review on Nanosuspension as a Novel Method for Solubility and Bioavailability Enhancement of Poorly Soluble Drugs

The formulation development of a drug is majorly based on the solubility of drugs. Nearly 40% of newly developed drugs show poor water solubility. Several approaches are used for the increasing solubility of such drugs for formulation development. Nanosuspension is one such attractive tactic which can be used for the enhancement of solubility, stability as well as bioavailability of such drugs. Nanosuspension can be defined as a two-phasic dosage form where solid drug particles of size less than 1 μm are dispersed in an aqueous phase with the help of a stabilizer. Particle size reduction in the nanoscale causes an increase in the surface area leading to an increase in dissolution rate and ultimately bioavailability is increased. A variety of excipients are used for the formulation of nanosuspension. Stabilizers, surfactants, co-surfactants, natural as well as organic solvents, buffers, salts, polyols, osmogents, and cryoprotectants are used in the formulation of nanosuspension. Various methods used in the formulation of nanosuspension can be classified into top-down and bottom-up approaches. Wet milling, high-pressure homogenization, anti-solvent techniques, melt emulsification, supercritical fluid extraction and ultrasonic homogenization are some of the methods for the preparation of nanosuspension. These methods are easy and appropriate for all poor water-soluble drugs. Nanosuspensions technology can be applied for the preparation of oral, pulmonary, injectable, ocular as well as targeted drug delivery. This review emphasizes various advantages and disadvantages of nanosuspension, its methods of preparation, formulation approaches, evaluation parameters, pharmaceutical applications, marketed products and patents of nanosuspension.

Insight into the Glycosylation Methods of the Flavonoids as an Approach to Enhance its Bioavailability and Pharmacological Activities

Abstract: Background: Flavonoids are a kind of polyphenol having a diverse set of pharmacological applications, but their bioavailability is limited due to their poor stability, poor solubility, quick clearance, and low intrinsic characteristics. According to the prior study, the flavonoids containing the sugar moiety have better solubility and stability (for example rutin) as they maintain greater plasma levels and a longer mean residence duration than the flavonoids have no glycoside moiety. Aim: This review focus on the enhancement of solubility and bioavailability of flavonoids by the various glycosylation techniques. Materials and Methods: In this review study, we discussed the various glycosylation approaches to improve solubility and bioavailability, such as microbial biotransformation, enzyme pathway manipulation, metabolic engineering, and chemical synthesis. Results: Glycosylation is one of the most efficient methods for increasing flavonoid solubility and stability, as a result the pharmacological activity also enhanced. The glycosylated compound such as scutellarin, quercetin 3-O-glucoside, Cyanidin 3-O-glucoside, kaempferitrin, baicalein 7-O-glucuronide and so on, shows the increased solubility and better pharmacological activities. Conclusion: The flavonoids need more attention to overcome their limitations, as they have plethora of applications on human health such as free radical scavenging property, anti-cancer activity, anti-diabetic, anti-inflammatory. Keywords: Flavonoids, Classification, Limitations, Bioavailability, Glycosylation.

An Ethereal Study of Drakshavaleha and Punarnavadi Mandura in Managing Pandu Roga with Special Reference to Iron Deficiency Anemia

Introduction: Anemia is a public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. We can find the references for numerous medications indicated for the treatment of Pandu in various treatises of Ayurveda. The formulations Punarnavadi Mandura and Drakshavaleha when administered in combination are supposed to act as iron and nutrition supplement, which will improve the overall health of the patients especially females of reproductive age group. Aim: The aim of the study was to evaluate the probable mode of action of Drakshavaleha and P. Mandura in Pandu Roga w.s.r to iron deficiency anemia. Materials and Methods: The information in this article is centered on various articles published in indexed and non-indexed journals of Ayurveda and Contemporary medical sciences, Ayurveda Samhitas, and their respective commentaries and textbooks of concerned subjects of both Ayurveda and Modern Medicine. Results: The ingredients of Drakshavaleha and P. Mandura mainly possess activities such as immunomodulatory, anti-oxidant, and bio-availability enhancers which can act collectively against the symptomatology of P. roga. Ingredients such as ManduraBhasma, Gomutra, Punarnava, Haridra, and Guda are proven to enhance the process of erythropoiesis. Conclusion: Based on the review, it can be considered that P. Mandura, a poly herb-mineral formulation and Drakshavaleha, a Naimittika Rasayana which can act as nutritional supplement, can counteract most of the pathological manifestations related to Pandu.

An Overview of Recent Patents and Future Perspective Based on Cyclodextrin Complexation.

The majority of drugs taken orally have limited aqueous solubility and dissolution rate. Cyclodextrin (CD) and its derivatives are used as pharmaceutical adjuvants, contributing to the development of safe and high bioavailability formulations. CDs have a unique structure with a variety of physicochemical features that aid pharmaceutical scientists in solving drug delivery issues for poorly water-soluble drugs (PWS). This article covers information about cyclodextrin and its various derivatives, its different manufacturing process, physicochemical properties, advantages, and recent advancements. There are various advantages of CD-based inclusion complexes, such as enhancement of solubility, bioavailability, and stability and reduction of irritation caused by the drug. Moreover, they are used as odor and taste enhancers and also prevent incompatibility by physically isolating the incompatible drug components in drug formulation. CD and its derivatives are extensively employed as solubilizers in the manufacturing of parenteral and oral dosage forms. Inclusion complexes formed by CDs with appropriately sized guest molecules improve drug water solubility, physical-chemical stability, and bioavailability. Simultaneously CDs prevent the drugs from degradation like oxidation, hydrolysis, and photodegradation and extend the shelf life of the drug. The manuscript also highlights patents and exclusive branded formulations of modified CDs. It also discusses the different examples of chemically modified CDs, i.e., captisol, sulfobutyl ether-β-CD, hydroxy propyl betadex, randomly methylated β-CD, methyl β-CD, and hydoxy propyl γ-CD, all are used in the various dosage forms.

Insights of Lipid-Based Drug Delivery Systems with an Emphasis on Quality by Design

Lipid-based drug delivery systems offer several advantages and have wide solubility, permeation, and bioavailability enhancement applications. This review provides detailed information on the fabrication, application and aspects of QbD of various lipid-based vesicles. Most of the review studies focused on lipid-based vesicles without the QbD aspect. This review article covers all the lipid-based systems in escalating on the method of QbD, which enhances the bioavailability of active pharmaceutical ingredients in different formulation approaches. Among all the different available approaches towards formulation development, lipid-based drug delivery systems (LBDDS) have continually maintained the limelight on themselves. One of the reasons for the popularity of LBDDS is their ability to solve problems with poorly water-soluble drugs and their bioavailability. Several drugs' efficacy was improved by utilizing this type of delivery system. Vesosomes, Phytosomes, Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), and Archaeosomes are novel lipid-based systems with unique applications in drug delivery. Hence, the present perspective is to review the various LBDDS approaches utilized to enhance the formulations' performance while dissecting the studies systematically to get a clear outline of various LBDD subsystems, their applications, methods of preparation, and the mechanism of drug delivery. In addition to this, the review also focuses on overcoming the lacunas of the past literature by making an attempt to identify Quality target product profile (QTPP), Critical quality attributes (CQAs) and applying them for the statistical design of experiments and continuous strategy by QbD at the same time harnessing their potential in risk assessment. Applying QbD in developing lipid-based drug delivery systems reduces the number of trials and yields a product with in-built quality as it deliberates various critical variables, process parameters, risk assessment, and control strategy in formulation development.

An overview of current strategies and future prospects in drug repurposing in tuberculosis

A large number of the population faces mortality as an effect of tuberculosis (TB). The line of treatment in the management of TB faces a jolt with ever-increasing multi-drug resistance (DR) cases. Further, the drugs engaged in the treatment of TB are associated with different toxicities, such as renal and hepatic toxicity. Different combinations are sought for effective anti-tuberculosis (anti-TB) effects with a decrease in toxicity. In this regard, drug repurposing has been very promising in improving the efficacy of drugs by enhancement of bioavailability and widening the safety margin. The success in drug repurposing lies in specified binding and inhibition of a particular target in the drug molecule. Different drugs have been repurposed for various ailments like cancer, Alzheimer’s disease, acquired immunodeficiency syndrome (AIDS), hair loss, etc. Repurposing in anti-TB drugs holds great potential too. The use of whole-cell screening assays and the availability of large chemical compounds for testing against Mycobacterium tuberculosis poses a challenge in this development. The target-based discovery of sites has emerged in the form of phenotypic screening as ethionamide R (EthR) and malate synthase inhibitors are similar to pharmaceuticals. In this review, the authors have thoroughly described the drug repurposing techniques on the basis of pharmacogenomics and drug metabolism, pathogen-targeted therapy, host-directed therapy, and bioinformatics approaches for the identification of drugs. Further, the significance of repurposing of drugs elaborated on large databases has been revealed. The role of genomics and network-based methods in drug repurposing has been also discussed in this article.

Insights on prospective role of Gallic acid as a Bioavailability Enhancer

The poor bioavailability of various drugs is the utmost obstacle in oral drug delivery. The use of natural bioenhancer as supplements with the primary therapeutic agent has gained wider acceptance and has been emerged as a potential method to increase the bioavailability of various drugs. Gallic acid is one of the chief phenolic natural compounds extensively distributed in plants and fruit. Despite its broad spectrum pharmacological effects, gallic acid significantly augments the bioavailability of diverse classes of drugs at low doses by impeding liver metabolism and altering gastrointestinal permeability. In this context, this review aims to summarise the promising bioavailability enhancing activity of gallic acid on different therapeutic agents. Furthermore, current evidence confirms that the intervention with gallic acid leads to enhance the bioavailability of various drugs; however, extensive research is need of the hour so that it could be utilized in drug formulations in the future for clinical use.

Enhancement of Glimepiride Bioavailability by Co-Crystallization Technique

Abstract: Drugs with low aqueous solubility show limited oral bioavaibility and dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization is a promising technique used to improve the oral solubility and dissolution rate of the drugs and hence their oral bioavailability. In general pharmaceutical co-crystals improve the physical properties such as crystallinity, solubility, wettability and dissolution behaviors of the drug without altering its pharmacological activity. The aim of this study was to enhance the solubility, dissolution rate and limited oral bioavailability of glimepiride (GLM) by cocrystallization with different carboxylic acid co-formers. Different co-crystal formulations were successfully prepared by ultrasound assisted suspension co-crystallization technique and then suspected to solubility study to choose the best formula to complete the study. Co-crystal of glimepiride -oxalic acid was characterized by X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and then further evaluated for dissolution behavior. The result showed that co-crystal could increase solubility and dissolution rate of glimepiride. The results of XRPD, FTIR and DSC indicating the presence of a new crystalline phase and formation of cocrystal while the SEM micrograph revealed the definite shape with crystalline composition of co-crystal. In vivo bioavailability study in rats showed higher Cmax , longer t1/2 el and MRT0-∞ and increased AUC0-∞ of 2.66 fold compared to the plain GLM. Therefore, co-crystallization technique can be expected to represent a promising tool for enhanced delivery of glimepiride.