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Biomedical subjects

R K Khar

Publications and source records attributed to R K Khar.

At least 19 recordsLinked to original sources
PubMed2007

Chitosan phthalate microspheres for oral delivery of insulin: preparation, characterization, and in vitro evaluation.

Chitosan phthalate polymer was synthesized and its microspheres were prepared by emulsion phase separation technique. The characterization of microspheres was determined by means of FTIR spectroscopy, electron microscopy, particle size, and zeta potential. The insulin was loaded to the microspheres by passive absorption technique. The peptic and tryptic enzymes degradation of insulin in microspheres was investigated. The in vitro release behavior of the microspheres was investigated under different pH conditions (pH 2.0 and pH 7.4). The degree of phthalate substitution in the synthesized polymer was 20%. The prepared microspheres were spherical with an average diameter 46.34 micro m. The insulin-loading capacity was 62%. Chitosan phthalate microspheres protect the insulin from gastric enzymes degradation that may enhance the oral stability of insulin. The encapsulated insulin was quickly released in a phosphate buffer saline (pH 7.4), whereas a small amount of insulin was released under acidic condition (0.1N HCl; pH 2.0) because under acidic conditions, carboxylic groups present in the system exist in nonionized form and are poorly hydrophilic. However, in alkaline conditions, it exists in ionized form and is considerably hydrophilic. The results suggest that chitosan phthalate microspheres may be used as a potential carrier for oral insulin delivery.

Administration, Oral↗
PubMed2006

Effect of DC/mDC iontophoresis and terpenes on transdermal permeation of methotrexate: in vitro study.

The systemic toxicity caused by methotrexate limits its use and transdermal delivery would be a possible alternative. Transdermal permeation of methotrexate loaded into polyacrylamide-based hydrogel patch, across mice skin was studied in vitro after pretreatment with terpenes and ethanol, alone or in combination with iontophoresis (DC/mDC). Polyacrylamide patches gave the maximum flux as compared to the copolymers of acrylamide and acrylic acid. Of the terpenes used, pure menthol showed maximum enhancement (38%), whereas pure limonene elicited a minimum of 9.9% enhancement. Binary combination of menthol and ethanol increased the permeation to 54.9%, which was further enhanced to 93.69% and 117% when used in combination with DC and square wave (mDC) iontophoresis, respectively. ATR-FTIR of the stratum corneum treated with terpenes showed a split in the asymmetric C-H stretching vibrations along with decrease in peak heights and areas of asymmetric, symmetric C-H stretching, C=O stretching and amide bands. A split in amide II band was observed with iontophoresis. ATR-FTIR studies suggest conformational changes in the lipid-protein domains thereby increasing permeation. Histopathological studies on treated skin samples, gave an insight about the anatomical changes brought by the application of various enhancers. Binary mixture of menthol and ethanol in combination with square wave gave best results.

Acrylic Resins↗
PubMed2005

Cyclodextrins in drug delivery: an updated review.

The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their use as excipients in drug formulation are also discussed in this article. The article also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting CDs in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.

Animals↗
PubMed2005

Stability-indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations.

A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of curcumin both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60 F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (9.25:0.75 v/v). This system was found to give compact spots for curcumin (R(f) value of 0.48 +/- 0.02). Densitometric analysis of curcumin was carried out in the absorbance mode at 430 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r = 0.996 and 0.994 with respect to peak height and peak area, respectively, in the concentration range 50-300 ng per spot. The mean value +/- S.D. of slope and intercept were 1.08 +/- 0.01, 51.93 +/- 0.54 and 8.39 +/- 0.21, 311.55 +/ -3.23 with respect to peak height and area, respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 8 and 25 ng per spot, respectively. Curcumin was subjected to acid and alkali hydrolysis, oxidation and photodegradation. The drug undergoes degradation under acidic, basic, light and oxidation conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and photo oxidation. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one.

Calibration↗
PubMed2005

Formulation and evaluation of an effective pH balanced topical antimicrobial product containing tea tree oil.

The effect of pH on the antimicrobial activity of Melaleuca alternifolia essential oil formulations was studied. Microemulsions, liposomal dispersions, multiple emulsions and a colloidal bed of sterile clay were formulated using 5% w/w of tea tree oil. A number of formulations were prepared at various pH values (5.0, 5.5, 6.0, 6.5, and 7.0). Thermal stability studies showed that the formulations were stable for more than eight months. Agar dilution tests showed MICs of 1.0% v/v S. aureus and S. epidermidis. In the broth dilution test, MBC of the oil for P. acnes was 0.5% v/v. MIC and MBC values were comparable to those of non-formulated tea tree oil, indicating that tea tree oil retained its activity in the above-mentioned formulations. The microbiological evaluation showed that the formulations containing 5% w/w tea tree oil had a maximum effect at pH 5.5.

Acne Vulgaris↗
PubMed2003

Targeted retentive device for oro-dental infections: formulation and development.

Fibers loaded with amoxycillin trihydrate were prepared for oro-dental infections using melt spinning technique. Ethylene vinyl acetate, a biocompatible polymer was used for providing controlled release effect over a period of several days. The fibers were evaluated for in vitro release in alkaline borate buffer pH 8.1 in a biological shaker which was rotated at 50 rpm at 37 degrees C. In situ studies were carried out in continuous flow through apparatus which simulated the conditions of periodontal pocket. Microbiological evaluation was carried out on strains commonly implicated in oro-dental infections namely S. aureus, S. mutans, and Bacteroides cereus. Results of in vitro release studies revealed that the effect was sustained over a period of 6 days and followed Fickian diffusion mechanism. In situ release study samples were well above the minimum inhibitory concentration of the drug. These samples were effective in inhibiting the growth of the above-mentioned strains. The optimized formulation was characterized for general appearance, content uniformity, and SEM. Stability studies carried out on the formulation showed the degradation rate constant value of 2.79 x 10(-4) per day. Retentive fibers were found to be very effective in controlled delivery of amoxycillin, and hence can be feasible alternative to systemic administration.

Amoxicillin↗
PubMed2001

Tetanus toxoid loaded 'preformed microspheres' of cross-linked dextran.

The conformation of an antigen and hence its biological activity may get compromised when encapsulated in controlled release microspheres during formulation. In order to obviate the need for exposure of the antigen to the inactivating conditions, such as exposure to organic solvent and the high shear stress of emulsification required for microencapsulation, an alternate strategy was employed. 'Pre-formed' microspheres (20--340 microm in size) made of cross-linked dextran (Dex) were employed as matrix for conjugation of tetanus toxoid (TT) under aqueous conditions. The native immunoreactivity of TT was completely retained after conjugation, as checked by immunofluorescence and quantitative ELISA. Immunogenicity of Dex--TT conjugate was tested in rodents. No untoward mortality or adverse effects of immunization with the test material were observed on histopathology of the site of injection. A single immunization with the long-acting depot formulation elicited anti-TT antibody response lasting for 1 year without any need of booster. The titres were comparable after 12 weeks with those obtained using the conventional alum adsorbed toxoid.

Animals↗
PubMed2001

Activity profile of glycolamide ester prodrugs of ibuprofen.

Glycolamide esters of ibuprofen (I), namely, unsubstituted (II), N,N dimethyl (III), and N,N diethyl (IV), were synthesized and studied for different physicochemical, pharmacological, and toxicological properties. They were comparable with I in respect of anti-inflammatory and analgesic activity but did not exhibit reduction in the ulcerogenicity on oral administration. However, all three exhibited significantly better topical activity in carrageenan-induced rat paw edema assay. In the same assay, they provided significant protection against inflammation when applied at a site remote to the inflammation site.

Administration, Oral↗
PubMed2001

Alkyl ester prodrugs for improved topical delivery of ibuprofen.

Topical delivery of ibuprofen directly to the site of inflammation can overcome gastrointestinal side effects associated with its long term oral administration. The set of physicochemical properties necessary for optimum topical delivery of ibuprofen can be imparted by formation of its ester prodrugs. Various alkyl ester prodrugs (methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-buty, n-pentyl, hexyl, heptyl, octyl, lauryl, cetyl and octadecyl esters) were synthesised and studied for their physicochemical properties and activity in the carrageenan induced rat paw oedema by topical route. Favourable shift in lipophilicity and self penetration enhancing effect of prodrugs responded in improved topical activity over the parent drug ibuprofen.

Administration, Topical↗
PubMed1998

Evaluation of hydrogel-based controlled-release niacin tablets.

Matrix-based controlled-release niacin tablets were formulated using guar gum. The effect on the in vitro dissolution profile was examined using variable guar gum content in the formulation. It was observed that the dissolution profile declined with the increase in the guar gum content in the tablet. The in vitro dissolution profile was also observed under different pH conditions and there was no marked change. The moisture content of granules also did not cause any considerable change in dissolution profile. Three different strength Niacin controlled-release tablets, including 500 mg, were prepared and it was found that applying the same variables of different guar gum content and moisture content of granules resulted in a very insignificant change in the in vitro dissolution profile. The experimental formulation compared well with commercial products and met the proposed standards for controlled-release products.

Chemistry, Pharmaceutical↗
PubMed1998

Evaluation of guar gum in the preparation of sustained-release matrix tablets.

Polymeric hydrophilic matrices are widely used for controlled-release preparations. The process of drug release is controlled by matrix swelling or polymer dissolution. It has been shown that the swelling of guar gum is affected by concentration of drug and viscosity grade of the polymer. This study examines the mechanism of behavior of guar gum in a polymer-drug matrix. The swelling action of guar gum, in turn, is controlled by the rate of water uptake into the matrices. An inverse relationship exists between the drug concentration in the gel and matrix swelling. This implies that guar gum swelling is one of the factors affecting drug release. The swelling behavior of guar gum is therefore useful in predicting drug release.

Biopharmaceutics↗
PubMed1998

Evaluation of buccoadhesive metronidazole tablets: microbiological response.

Metronidazole has been found beneficial in a number of oro-dental infections namely dry socket, gingivitis, smelling tumours and periodontal diseases where anaerobes are implicated as pathogens. Buccoadhesive tablets of metronidazole were prepared by compressing the drug, bioadhesive polymers namely Carbopol-934P, a cellulose ether derivative, mannitol and suitable flavouring and sweetening agents. The tablet showed good release in vitro. It was subjected to in-situ release studies using bovine cheek pouch membrane in a flow through cell. The concentration was found to be above the MIC of the drug over the entire period of the release studies. The samples were tested against anaerobic strains commonly found in oro-dental infections. Since anaerobes are very slow growing microorganisms, a method for testing their susceptibility to metronidazole solutions was developed which can be used for other bioadhesive formulations which are active against anaerobes.

Adhesives↗
PubMed1998

Formulation and characterisation of a buccoadhesive erodible tablet for the treatment of oral lesions.

Buccoadhesive erodible tablets of trimcinolone acetonide were prepared using different bioadhesive polymers along with excipients like mannitol and PEG-6000. In vitro release characteristics were evaluated using a 'flow-thru assembly' which simulated the conditions of the human buccal cavity. The bioadhesive performance and the surface pH of the tablets was satisfactory. The optimized formulation containing 8.0 mg of triamcinolone acetonide, 2.5 mg of mannitol, 7.5 mg of PEG-6000, 2.0 mg of magnesium stearate along with carbopol-934P (CP-934P) and sodium carboxy methyl cellulose-DVP (SCMC-DVP) in the ratio of 1:4 was found to release the drug for a period of over 8 h without getting dislodged. Maximum in vitro drug release was found to be 79.08% in 8 h study. In vivo evaluation of placebo buccoadhesive tablets revealed adequate comfort, taste, non-irritancy during the period of study. None of the volunteers reported severe dry mouth/severe salivation or heaviness at the place of attachment. A linear and positive correlation was found between in vitro and in vivo mean adhesion time. The buccoadhesive tablet eroded completely after 8 h leaving no exhausted device to be removed. This formulation has potential clinical usefulness for the treatment of oral lesions.

Adhesives↗
PubMed1997

Long-term high immune response to diphtheria toxoid in rodents with diphtheria toxoid conjugated to dextran as a single contact point delivery system.

Cross-linked dextran beads were used as a carrier for development of a 'single-contact' vaccine delivery system. Diphtheria toxoid (DT) was covalently coupled to dextran beads (DEX-DT conjugate). The conjugate was immunoreactive with antibodies raised against native DT. Immunization of rats with DEX-DT conjugate generated on average 24 times higher antibody titres against diphtheria toxoid than immunization with the conventional DT absorbed on alum. The immune response was sustained for 9 months, with gradual decline of antibody titres thereafter. Significant antibody titres were measurable in rats after 1 year of immunization. DEX-DT had neither acute nor long-term adverse effects on the health of animals, as evidenced by local reactions, general behaviour, food intake, body weight gain and survival compared with controls.

Animals↗
PubMed1994

Effect of group substitution on the physicochemical properties of ibuprofen prodrugs.

A series of alkyl ester prodrugs of ibuprofen was synthesized and studied for its physicochemical properties like aqueous solubility, octanol-water partition coefficient and hydrolysis kinetics in aqueous buffer and human plasma. These physicochemical parameters have a forebearing on the overall activity profile of these prodrugs. Mathematical relationships have been derived to characterize these properties.

Chemical Phenomena↗
PubMed1993

Evaluation of sterically stabilized liposomes as a vehicle for targeting technetium-99m labelled radiopharmaceuticals.

Sterically stabilized neutral liposomes (multilamellar vesicles) were prepared by sonicating phosphatidylcholine and cholesterol (molar ratio 4:1) film in phosphate buffered saline (50 mM, pH 7.4) containing 4% Tween 20. Tc-99m-GHA was incorporated in these liposomes by treating 0.5 ml of the suspension with lyophilized GHA kit (5 mg GHA and 250 micrograms SnCl2 x 2 H2O) followed by addition of 1 ml 99mTcO4- (1-3 mCi). The labelling yield was 60-70%. Tween 20 has provided significant stability of the radiolabel as compared to that without its addition, when radiolabelled liposomes were incubated in serum up to 24 h. With respect to Tc-99m-GHA alone, radiolabelled liposomes exhibited 4- to 6-fold greater radioactivity in the blood of rabbits (15 min-24 h). Comparison of biodistribution data of radiolabelled liposomes and Tc-99m-GHA in mice demonstrated a 10- to 12-fold greater hepatic accumulation of radiolabelled liposomes with respect to that of Tc-99m-GHA throughout the period of study (15 min-24 h), though their concentration in the kidneys was comparable.

Animals↗
PubMed1990

In vitro and in vivo studies of sustained-release floating dosage forms containing salbutamol sulfate.

Peroral sustained-release floating capsules containing salbutamol sulfate were formulated using different combinations of hydrocolloids of natural and semi-synthetic origin. The floating properties and release rate characteristics were determined for the capsules in simulated gastric fluid USP XXI and HCl (0.1 mol.l-1) as dissolution media. Also, a marketed sustained-release non-floating capsule containing salbutamol sulfate was studied for its release rate characteristics. The floating capsule formulated showed a Higuchian release profile while the marketed product released only about 80% of the total dose in the stipulated 12 h in the dissolution medium. In vivo X-ray studies of the abdomen were carried out to locate the floating and non-floating (fabricated) dosage forms at various time intervals of uniform duration. The floating capsule definitely indicated a residence time (up to 8-9 h) in the stomach greater than for the non-floating capsule.

Albuterol↗