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1.
Heliyon ; 10(7): e29044, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601602

ABSTRACT

Cloud computing has emerged as a transformative force in healthcare and biomedical sciences, offering scalable, on-demand resources for managing vast amounts of data. This review explores the integration of cloud computing within these fields, highlighting its pivotal role in enhancing data management, security, and accessibility. We examine the application of cloud computing in various healthcare domains, including electronic medical records, telemedicine, and personalized patient care, as well as its impact on bioinformatics research, particularly in genomics, proteomics, and metabolomics. The review also addresses the challenges and ethical considerations associated with cloud-based healthcare solutions, such as data privacy and cybersecurity. By providing a comprehensive overview, we aim to assist readers in understanding the significance of cloud computing in modern medical applications and its potential to revolutionize both patient care and biomedical research.

2.
Heliyon ; 10(2): e24210, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38304764

ABSTRACT

Plasticizers are employed to stabilize films by safeguarding their physical stability and avoiding the degradation of the loaded therapeutic drug during processing and storage. In the present study, the plasticizer effect (glycerol) was studied on bioadhesive films based on sodium alginate (SA), carboxymethyl cellulose (CMC) and gelatin (GE) polymers loaded with amphotericin B (AmB). The main objective of the current study was to assess the morphological, mechanical, thermal, optical, and barrier properties of the films as a function of glycerol (Gly) concentration (0.5-1.5 %) using different techniques such as Scanning Electron Microscope (SEM), Texture analyzer (TA), Differential Scanning Calorimeter (DSC), X-Ray Diffraction (XRD), and Fourier Transforms Infrared Spectroscopy (FTIR). The concentration increase of glycerol resulted in an increase in Water Vapor Permeability (WVP) (0.187-0.334), elongation at break (EAB) (0.88-35.48 %), thickness (0.032-0.065 mm) and moisture level (17.5-41.76 %) whereas opacity, tensile strength (TS) (16.81-0.86 MPa), and young's modulus (YM) (0.194-0.002 MPa) values decreased. Glycerol incorporation in the film-Forming solution decreased the brittleness and fragility of the films. Fourier Transform Infrared (FTIR) spectra showed that intermolecular hydrogen bonding occurred between glycerol and polymers in plasticized films compared to control films. Furthermore, molecular docking was applied to predict the binding interactions betweem AmB, CMC, gelatin, SA and glycerol, which further endorsed the stabilizing effects of glycerol in the complex formation between AmB, CMC, SA, and gelatin. The Findings of the current study demonstrated that this polymeric blend could be used to successfully prepare bioadhesive films with glycerol as a plasticizer.

3.
Life (Basel) ; 13(1)2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36675973

ABSTRACT

Brain tumors are a widespread and serious neurological phenomenon that can be life- threatening. The computing field has allowed for the development of artificial intelligence (AI), which can mimic the neural network of the human brain. One use of this technology has been to help researchers capture hidden, high-dimensional images of brain tumors. These images can provide new insights into the nature of brain tumors and help to improve treatment options. AI and precision medicine (PM) are converging to revolutionize healthcare. AI has the potential to improve cancer imaging interpretation in several ways, including more accurate tumor genotyping, more precise delineation of tumor volume, and better prediction of clinical outcomes. AI-assisted brain surgery can be an effective and safe option for treating brain tumors. This review discusses various AI and PM techniques that can be used in brain tumor treatment. These new techniques for the treatment of brain tumors, i.e., genomic profiling, microRNA panels, quantitative imaging, and radiomics, hold great promise for the future. However, there are challenges that must be overcome for these technologies to reach their full potential and improve healthcare.

4.
Daru ; 29(2): 241-253, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34417727

ABSTRACT

PURPOSE: Effective remedy to gastrointestinal (GI) side effects caused by poorly water-soluble drugs remains a challenge. Researching for novel techniques to reduce these side effects and increase patient adherence to medical treatment is of interest. The current study aims to develop an innovative nano-sized gastro-retentive drug delivery for better management of poorly water-soluble drugs. METHOD: A non-disintegrating ibuprofen-asymmetric membrane floating nanoparticle (Ibuprofen-AMFNP) was prepared by phase inversion technique to increase the gastric residence of the drug. Powder characterization, solubility, in vitro buoyancy, effect on in vivo inflammatory markers, and polymer diffusibility studies were conducted on the prepared formulation. All UV-spectrophotometric analysis was accomplished through a fiber optic system. RESULTS: The prepared Ibuprofen-AMFNPs were in the nano range of 114.45 nm ±1.31 nm. The formulation was buoyant for 12 h in the dissolution media indicating increased gastric residence, had better solubility and powder characteristics compared to the pure drug. Scanning electron microscopy revealed an outer non-porous and inner porous asymmetric membrane. Ibuprofen-AMFNP followed Higuchi drug release kinetics (p=0.9925) and had a Fickian diffusion release mechanism (n=0.05). Polymer diffusibility study showed that the 24 h stored formulation had faster drug release with no lag time (-923.08 nm/h) compared to a fresh formulation (2526.32 nm/h). The prepared nano-formulation showed a higher percentage of anti-inflammatory (85.144%) effect compared to the pure drug (78.336%). CONCLUSION: Ibuprofen-AMFNP is envisioned to help reduce drug-related GI side effects, improve drug delivery, and thereby increase patient adherence to medical treatment.


Subject(s)
Drug Compounding/methods , Ibuprofen/chemical synthesis , Water/chemistry , Delayed-Action Preparations , Drug Delivery Systems , Ibuprofen/chemistry , Microscopy, Electron, Scanning , Nanoparticles , Particle Size , Solubility
5.
Curr Pharm Des ; 17(15): 1512-6, 2011.
Article in English | MEDLINE | ID: mdl-21501113

ABSTRACT

Drugs for several diseases are still given without regard to the time of the day. Variation in dosing time is generally related with the effectiveness and toxicity of many drugs. On the other hand, several drugs affect the circadian clock. The knowledge of interactions between the circadian clock and drugs is valuable in clinical practice. The pharmacodynamics and pharmacokinetics of the medication influence the chronopharmacological phenomena and recent advances in it have made the traditional goal of pharmaceutics rather outdated. Enhanced progress in chronopharmacotherapy can be achieved if an identification of a rhythmic marker for selecting dosing time is done. However, technology involved in development of drug delivery systems (DDS) that match the circadian rhythm, and the unraveling of the relationship between circardian clock and pathology may be the hindrance in its prosperity for now. The Chronopharmaceutical Drug Delivery System (CDDS) has emerged during the last decade as a possible drug delivery system against several diseases, which may lead to the creation of a sub-disciple of pharmaceutics to be explored called 'chronopharmaceutics'. The review addresses the approaches to this sub-discipline, call attention to potential disease-targets, identifies existing technologies, hurdles and future of chropharmaceuticals. Chronopharmaceuticals coupled with nanotechnology could be the future of DDS, and lead to safer and more efficient disease therapy in the future.


Subject(s)
Drug Chronotherapy , Drug Delivery Systems/trends , Pharmaceutical Preparations/administration & dosage , Animals , Drug Design , Humans , Nanotechnology/methods , Nanotechnology/trends
6.
PDA J Pharm Sci Technol ; 65(1): 32-41, 2011.
Article in English | MEDLINE | ID: mdl-21414938

ABSTRACT

In the present study, an in situ nondisintegrating polymeric capsular system in achieving delayed as well as improved osmotic flow for the model drug cefadroxil was developed. In situ formed asymmetric membrane capsule was prepared by precipitation of the asymmetric membrane (AM) on the walls of conventional hard gelatin capsules in fabricated glass holders via a dry phase inversion process. The effect of different formulation variables were studied based on a 2(3) factorial design as one variable changed from one level to another, namely, the level of osmogen, ethylcellulose, and pore former, apart from studying the effect of varying osmotic pressure and agitation intensity on drug release. Scanning electron microscopy showed an outer, dense, non-porous region and an inner, lighter, porous region for the prepared AM inside, and a gelatin layer outside. Statistical testing (Dunnett multiple comparison test) was applied for in vitro drug release (n = 6) at P < 0.05. The best formulation in the design closely corresponded to the extra design checkpoint formulation by a similarity (f(2)) value of 96.18. The drug release was independent of the agitation intensity but dependent on the osmotic pressure of the dissolution media. The release kinetics followed the Higuchi model, and the mechanism of release was Fickian diffusion. LAY ABSTRACT: The asymmetric membrane capsule (AMC) is a unique drug delivery system that looks like a conventional hard gelatin capsule but has significant advantages over it. In the present study, a system was made that had an outer disintegrating hard gelatin capsule and an inner nondisintegrating polymeric capsular system for delivering a model drug cefadroxil. The inner nondisintegrating polymeric capsular system was the AMC, which was prepared by precipitation of the asymmetric membrane (AM) on the walls of conventional hard gelatin capsules in fabricated glass holders via a dry phase inversion process. The effect of different formulation variables that might affect the drug release were studied based on a 2(3) factorial design. The formulation variables were level of osmogen, ethylcellulose, and pore former. The effect of varying osmotic pressure and agitation intensity on drug release was also studied. Scanning electron microscopy showed an outer, dense, nonporous region and an inner, lighter, porous region for the prepared AM inside, and a gelatin layer outside. Statistical testing was applied for in vitro drug release. Results showed the drug release to be independent of the agitation intensity but dependent on the osmotic pressure of the dissolution media. The release kinetics followed the Higuchi model, and the mechanism of release was Fickian diffusion.


Subject(s)
Capsules , Solubility , Cefadroxil , Drug Delivery Systems , Microscopy, Electron, Scanning , Osmosis , Osmotic Pressure
7.
Pharm Dev Technol ; 16(5): 457-65, 2011 Oct.
Article in English | MEDLINE | ID: mdl-20482448

ABSTRACT

In the present study, an intestinal pH, disintegrating and non-disintegrating dual capsular system using formaldehyde vapor and phase transition technique, respectively, was developed to achieve delayed as well as improved osmotic flow for the model drug cefadroxil. Formaldehyde vapor was used to attain gastric resistance to the outer gelatin capsule, which disintegrated at the intestinal pH to give a non-disintegrating asymmetric membrane capsule (AMC). The AMC was prepared via dry phase inversion process. The effects of different formulation variables were studied based on 2³ factorial design, namely, level of osmogen, ethylcellulose, and pore former, apart from studying the effects of varying osmotic pressure, agitation intensity, and intentional defect on drug release. Scanning electron microscopy showed an outer dense non-porous and an inner lighter porous region for the prepared asymmetric membrane. Statistical test was applied for in-vitro drug release at P > 0.05. The best formulation in the design closely corresponded to the extra design checkpoint formulation by a similarity (f2) value of 95.28. The drug release was independent of the agitation intensity and intentional defect of the film but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed zero-order, and mechanism of release was Fickian diffusion.


Subject(s)
Capsules/chemistry , Cefadroxil/chemistry , Delayed-Action Preparations/chemistry , Gelatin/chemistry , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Capsules/administration & dosage , Cefadroxil/administration & dosage , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Data Interpretation, Statistical , Delayed-Action Preparations/administration & dosage , Gelatin/administration & dosage , Hydrogen-Ion Concentration , Kinetics , Microscopy, Electron, Scanning , Osmosis , Osmotic Pressure , Phase Transition , Porosity , Solubility
8.
Curr Drug Deliv ; 7(3): 230-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20497101

ABSTRACT

In the present study, a phase transited nondisintegrating polymeric capsular system in achieving delayed as well as improved osmotic flow for the model drug cefadroxil was developed. Asymmetric membrane capsule (AMC) was prepared by precipitation of asymmetric membrane (AM) on the fabricated glass mold pins via wet phase inversion process. Effect of different formulation variables were studied based on 23 factorial design, namely, level of osmogen, ethylcellulose, pore former, apart from studying the effect of varying osmotic pressure on drug release. Scanning electron microscopy showed an outer dense non-porous region and an inner lighter porous region for the prepared AMC. Statistical test (Dunnett multiple comparison test) was applied for in vitro drug release (n=6) at P < 0.05. The best formulation in the design closely corresponded to the extra design checkpoint formulation by a similarity factor (f2) of 98.91, and a difference factor (f1) of 2.17. The drug release was independent of agitation intensity but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed Higuchi model, and mechanism of release was Fickian diffusion.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cefadroxil/chemistry , Cellulose/analogs & derivatives , Drug Carriers , Drug Delivery Systems/instrumentation , Membranes, Artificial , Anti-Bacterial Agents/chemistry , Capsules , Cefadroxil/administration & dosage , Cellulose/chemistry , Chemistry, Pharmaceutical , Delayed-Action Preparations , Diffusion , Excipients/chemistry , Kinetics , Microscopy, Electron, Scanning , Models, Chemical , Models, Statistical , Osmotic Pressure , Phase Transition , Porosity , Solubility , Surface Properties
9.
Oman Med J ; 25(2): 79-87, 2010 Apr.
Article in English | MEDLINE | ID: mdl-22125706

ABSTRACT

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery) namely prodrugs, pH and time dependent systems, and microbially triggered systems, which achieved limited success and had limitations as compared with newer CDDS namely pressure controlled colonic delivery capsules, CODESTM, and osmotic controlled drug delivery which are unique in terms of achieving in vivo site specificity, and feasibility of manufacturing process.

10.
J Drug Target ; 17(3): 235-41, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19558362

ABSTRACT

In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with L-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug.


Subject(s)
Colitis/drug therapy , Glycine/administration & dosage , Ketoprofen/administration & dosage , Prodrugs/chemical synthesis , Acetic Acid/adverse effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colitis/chemically induced , Glycine/chemistry , Ketoprofen/chemistry , Prodrugs/therapeutic use , Random Allocation , Rats , Sulfasalazine/therapeutic use
11.
Pharm Dev Technol ; 14(5): 540-7, 2009.
Article in English | MEDLINE | ID: mdl-19552562

ABSTRACT

Buccoadhesive gels for transbuccal delivery of glipizide were prepared using different bio-adhesive polymers. The gels were prepared by solution polymerization technique. An apparatus simulating the in vivo conditions of the mouth was designed in order to assess in vitro drug release kinetics of these gels. The gels were also evaluated for spreadability, buccoadhesive strength, swelling index, and viscosity. Maximum buccoadhesive strength was observed for formulation, F8 with good sustained release behavior, whereas viscosity and swelling index was highest for the formulation, F5 but with minimum buccoadhesive strength. The drug release kinetics followed Higuchi model with release mechanism being Fickian diffusion.


Subject(s)
Delayed-Action Preparations/chemistry , Gels/chemistry , Glipizide/administration & dosage , Hypoglycemic Agents/administration & dosage , Adhesiveness , Administration, Buccal , Animals , Chemistry, Pharmaceutical/instrumentation , Egg Shell/metabolism , Equipment Design , Membranes/metabolism , Polymers/chemistry , Viscosity , Water/chemistry
12.
Drug Dev Ind Pharm ; 34(7): 735-43, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18608466

ABSTRACT

A phase-transited, nondisintegrating, controlled release, asymmetric membrane capsular system for poorly water-soluble model drug flurbiprofen was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. Asymmetric membrane capsules (AMCs) were prepared using fabricated glass mold pins through wet phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies for all the prepared formulations were carried out (n = 6). Statistical test was applied for in vitro drug release at p > .05. Predicted in vivo concentration from in vitro release data closely matched the minimum effective concentration (in vivo) level achieved by the drug from its release through phase-transited AMC in rabbits for the first hour. The drug release was found to be independent of the pH but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed level A correlation (R(2) > .99) with 42.84% relative bioavailability compared to immediate release tablet of flurbiprofen. Excellent correlation achieved suggested that the in vivo performance of the AMCs could be accurately predicted from their in vitro release profile.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Flurbiprofen/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Biological Availability , Capsules , Delayed-Action Preparations , Female , Flurbiprofen/administration & dosage , Flurbiprofen/chemistry , Hydrogen-Ion Concentration , Male , Microscopy, Electron, Scanning , Osmosis , Osmotic Pressure , Rabbits , Solubility
13.
AAPS PharmSciTech ; 9(1): 60-6, 2008.
Article in English | MEDLINE | ID: mdl-18446462

ABSTRACT

In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2(3) factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50 degrees C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology and kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin and various excipients used in the tablet formulation. Stability studies carried out as per ICH Q(1) A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming and disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.


Subject(s)
Combinatorial Chemistry Techniques/methods , Drug Carriers/chemistry , Drug Compounding/methods , Drug Design , Excipients/chemistry , Indomethacin/chemistry , Administration, Oral , Drug Evaluation, Preclinical , Indomethacin/administration & dosage , Pediatrics , Quality Control , Tablets/chemistry
14.
AAPS PharmSciTech ; 9(1): 87-94, 2008.
Article in English | MEDLINE | ID: mdl-18446466

ABSTRACT

The purpose of this study was to develop a dosage form that was easy to administer and provides rapid release of the drug roxithromycin, using modified polysaccharides as rapidly disintegrating excipients. Modified polysaccharides co grinded treated agar (C-TAG) and co grinded treated guar gum (C-TGG) were prepared by subjecting pure polysaccharides namely agar and guar gum respectively to sequential processes of wetting, drying and co grinding with mannitol (1:1). The modified polysaccharides were characterized by Scanning Electron Microscopy and Diffuse Reflectance Spectroscopy and evaluated for particle size distribution, derived properties, swelling index and biodegradability. Optimization studies based on 2(2) factorial designs, with friability and disintegration time as response parameters were used to formulate orodispersible tablets of roxithromycin and evaluated for wetting time, water absorption ratio and in vitro drug release at salivary pH 6.4 and physiological pH 7.4. Results indicated that lower levels of modified polysaccharides namely C-TAG in F(3) and C-TGG in F(7) and higher levels of microcrystalline cellulose, exhibited least disintegration times without friability concerns. In vitro release of optimized formulations F(3) and F(7,) both at salivary pH and physiological pH was found to be more than 90% within 30 min as compared to 27.82% at the same time point of conventional formulation. Stability studies carried out as per ICH Q1A guidelines suggested the formulations to be stable for a period of 6 months. Thus the approach of using modified polysaccharides as fast disintegrating excipient can be used to formulate a stable orodispersible formulation.


Subject(s)
Drug Carriers/chemistry , Excipients/chemistry , Polysaccharides/chemistry , Roxithromycin/chemistry , Administration, Oral , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Drug Compounding/methods , Drug Design , Drug Evaluation, Preclinical/methods , Roxithromycin/administration & dosage , Tablets
15.
Curr Drug Deliv ; 5(2): 127-32, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18393815

ABSTRACT

An in situ formed non-disintegrating controlled release asymmetric membrane capsular system, offering improved osmotic effect, was used to deliver poorly water soluble drug flurbiprofen (model drug) to demonstrate how controlled release characteristics could be manipulated by design of polymeric capsule with an asymmetric membrane. In situ formed asymmetric membrane capsule was made by dry method via precipitation of asymmetric membrane on the walls of hard gelatin capsule. Effect of different formulation variables were studied based on 2(3) factorial design, namely, level of osmogen, ethylcellulose and pore former apart from studying the effect of varying osmotic pressure on drug release. Scanning Electron Microscopy showed an outer dense non porous region and an inner lighter porous region for the prepared asymmetric membrane inside and a gelatin layer outside. Statistical test (Dunnett Multiple Comparison Test) was applied for in vitro drug release at P>0.05. The best formulation closely corresponded to the extra design checkpoint formulation by a similarity (f(2)) value of 96.88. The drug release was independent of pH but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed Higuchi model and mechanism of release was Fickian diffusion.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Flurbiprofen/pharmacokinetics , Membranes, Artificial , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Capsules , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemical Precipitation , Data Interpretation, Statistical , Delayed-Action Preparations , Flurbiprofen/administration & dosage , Gelatin/chemistry , Hydrogen-Ion Concentration , Microscopy, Electron, Scanning , Osmosis , Osmotic Pressure , Solubility
16.
J Pharm Pharmacol ; 60(5): 607-13, 2008 May.
Article in English | MEDLINE | ID: mdl-18416937

ABSTRACT

The carboxylic group responsible for the gastric side-effects of the propionic acid derivative, flurbiprofen, was masked temporarily to overcome these side-effects and to accomplish colon-specific delivery of the drug. An amide prodrug (FLU-GLY) was synthesized by coupling flurbiprofen with L-glycine. Confirmation and characterization of the structure of the synthesized prodrug included elemental analysis, Fourier transform (FT)-IR, FT-NMR, mass (FAB) spectroscopy, and determinations of R(f), R(t) and R(M) values, respectively. Aqueous solubility and lipophilicity (logP) value were determined at pH 1.2, 4.0, 6.8 and 7.4. In-vitro reversion of FLU-GLY to flurbiprofen was measured at different pHs and in a simulated colonic environment. Acute toxicity and ulceration potential were evaluated in-vivo in albino rats. Pre-formulation studies showed increased hydrophilicity but a non-significant increase in lipophilicity of the prodrug. In-vitro reversion studies suggested that the prodrug remained intact until colonic pH was attained, when the colonic microfloral enzymes (amidase) hydrolysed the FLU-GLY amide linkage, releasing the free drug. In-vivo evaluation indicated that the prodrug was much less toxic and had less ulcerogenic activity than the parent drug. Selective delivery of drugs to the colon can be useful in terms of reducing the dose administered and reducing undesirable side-effects.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Drug Delivery Systems , Flurbiprofen/administration & dosage , Glycine/administration & dosage , Prodrugs/administration & dosage , Stomach/drug effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Colon , Female , Flurbiprofen/chemistry , Flurbiprofen/toxicity , Glycine/chemistry , Glycine/toxicity , Male , Prodrugs/chemistry , Prodrugs/toxicity , Rats , Solubility , Stomach/pathology , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology
17.
Eur J Pharm Biopharm ; 69(2): 658-66, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18206358

ABSTRACT

In the present study, both disintegrating and non-disintegrating polymeric capsular system in achieving delayed as well as improved osmotic flow for the model drug cefadroxil was developed. Asymmetric membrane in membrane capsule (AMMC) was prepared on a glass mold pin via phase inversion process in two steps. Step 1 included formation of a non-disintegrating, asymmetric membrane capsule (AMC) and step 2 involved formation of a pH sensitive, disintegrating, asymmetric membrane (AM) formed over the non-disintegrating membrane. The effects of different formulation variables were studied namely, level of osmogen, membrane thickness, and level of pore former. Effects of varying osmotic pressure, agitational intensity and intentional defect in the inner membrane on drug release were also studied. Membrane characterization by scanning electron microscopy showed dense regions with less pores on the outer surface of the disintegrating membrane and porous regions on the inner surface of the non-disintegrating asymmetric membrane. In vitro release studies for all the prepared formulations were done (n=6). The drug release was independent of pH, agitational intensity and intentional defect on the membrane but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed the zero order and the mechanism of release was Fickian diffusion.


Subject(s)
Anti-Bacterial Agents/chemistry , Cefadroxil/chemistry , Anti-Bacterial Agents/administration & dosage , Capsules , Cefadroxil/administration & dosage , Chemistry, Pharmaceutical , Kinetics , Membranes, Artificial , Microscopy, Electron, Scanning , Osmosis , Osmotic Pressure , Solubility
18.
PDA J Pharm Sci Technol ; 62(6): 421-8, 2008.
Article in English | MEDLINE | ID: mdl-19634345

ABSTRACT

A passage-delaying, multiple unit, controlled release system of loratadine was designed to increase residence time in the stomach involving minimum contact with the gastric mucosa. Oil-entrapped floating microbeads prepared using the emulsion gelation method were optimized by a 2(3) factorial design and a polymer ratio of 1.5:0.5 (casein:sodium alginate) by weight, and 15% w/v of oil (mineral oil/castor oil) and 1 M calcium chloride solution were selected as the optimized processing conditions for the desired buoyancy and physical stability. In vitro drug release in acid phthalate buffer, pH 3.12, demonstrated a sustained release for 8 h that best fitted the peppas model with n < 0.45. The ethylcellulose coating of the passage-delaying microbeads optimized by a 2(2) factorial design resulted in a controlled release formulation of loratadine that provided zero-order release for 8 h.


Subject(s)
Loratadine/administration & dosage , Microspheres , Calorimetry, Differential Scanning , Delayed-Action Preparations , Hydrogen-Ion Concentration , Loratadine/chemistry , Solubility
19.
AAPS PharmSciTech ; 7(3): 56, 2006 Jul 07.
Article in English | MEDLINE | ID: mdl-17025237

ABSTRACT

A nondisintegrating, controlled release, asymmetric membrane capsular system of flurbiprofen was developed and evaluated for controlled release of the drug to overcome some of its side effects. Asymmetric membrane capsules were prepared using fabricated glass mold pins by phase inversion process. The effect of different formulation variables was studied based on 2(3) factorial design; namely, level of osmogen, membrane thickness, and level of pore former. Effects of polymer diffusibility and varying osmotic pressure on drug release were also studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. Differential scanning calorimetry studies showed no incompatibility between the drug and the excipients used in the study. In vitro release studies for all the prepared formulations were done (n = 6). Statistical test (Dunnett multiple comparison test) was applied for in vitro drug release at P > .05. The best formulation closely corresponded to the extra design checkpoint formulation by a similarity (f2) value of 92.94. The drug release was independent of pH but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed the Higuchi model and the mechanism of release was Fickian diffusion.


Subject(s)
Chemistry, Pharmaceutical , Delayed-Action Preparations , Pharmaceutical Preparations/administration & dosage , Pharmacokinetics , Capsules/chemistry , Drug Delivery Systems , Membranes/chemistry , Osmosis , Permeability , Pharmaceutical Preparations/chemistry , Solubility
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