Development of matrix type transdermal patches of lercanidipine hydrochloride: physicochemical and in-vitro characterization

Background and the purpose of the study

Lercanidipine hydrochloride (LRDP) is used in the treatment of hypertension because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS) of LRDP and to determine the effect of penetration enhancer, limonene on drug permeation

Methods

The matrix type TDDS of LRDP were prepared by solvent evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of Eudragit RL100 (ERL) and hydroxypropyl methyl cellulose (HPMC) in 1.5:8.5, 3:7, 4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried 10 mg of LRDP/patch area, 8% v/w of d-limonene as a penetration enhancer, 20% v/w of propylene glycol as plasticizer in methanol and dichloromethane as solvent system. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation studies were carried out across excised rat skin using Franz diffusion cell.

Results

All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 24 hrs from the six formulations were 82.0%, 74.9%, 63.2%, 63.5%, 59.8% and 53.5% respectively. Corresponding values for the cumulative amounts of the drug permeated across the rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5 and 1663.4 µg/cm² respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of the drug release was diffusion mediated. The patches were seemingly free of potentially hazardous skin irritation.

Conclusions

The patches composed of ERL, HPMC (1.5:8.5) with 8% v/w limonene as penetration enhancer may be selected for the development of TDDS of LRDP for potential therapeutic use by using a suitable adhesive layer and backing membrane.     

Enhance transdermal delivery of flurbiprofen via microemulsions: Effects of different types of surfactants and cosurfactants

Background and the purpose of the study

Microemulsions are thermodynamically stable, clear dispersions of water, oil, surfactant, and cosurfactant. This study was aimed to develop flurbiprofen microemulsion for enhanced transdermal delivery and investigate the effects of different surfactants and cosurfactants on its delivery and phase behavior.

Method

Various surfactant-cosurfactant mixtures in ratio of 2:1 (Smix) along with oleic acid (oil) were selected and phase diagrams were constructed. Six microemulsions each containing 5% drug, 5% oil, 56% Smix and 34% water, were prepared and compared for their permeation and phase behaviors to determine the effects of the type of Smix.

Results

In vitro transdermal permeation through rabbit skin of all microemulsions was high than saturated aqueous drug solution. Tween 20 and ethanol as Smix produced the highest flux amongst all the Smix, and were used to prepare formulations with different values of oil and Smix. While the type of surfactant did not affect the droplet size, propylene glycol as cosurfactant produced the largest droplets and highest viscosity. Decrease in oil or Smix concentration resulted in decrease of the droplet size and increase in permeation flux while decrease in viscosity also increased the permeation flux of microemulsions. Finally the selected microemulsion formulation comprising 5% flurbiprofen, 5% oleic acid, 46% Tween 20:ethanol (2:1) and 44% water, showed the highest transdermal flux and caused no skin irritation.

Conclusion

Type of surfactant and cosurfactant affect both the phase behavior and transdermal drug delivery of microemulsion; and results of this study showed that they are promising vehicles for improved transdermal delivery and sustained action of flurbiprofen.     

Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

Background and the purpose of the study

Domperidone (DOM) is a dopamine- receptor (D₂) antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN) and Nanostructured Lipide Carrier (NLC). The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN) and DOM loaded nanostructured lipid carriers (DOM-NLC).

Methods

DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99%) and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM). SLN and NLC formulations were subjected to stability study over a period of 40 days.

Results

The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1) and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84% and 32.23 nm, 0.160, 10.47 mV, 90.49% respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P<0.05) change in particle size, zeta potential, PDI and entrapment efficiency indicating the developed SLN and NLC were fairly stable.

Conclusion

Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could be prepared by hot homogenization followed by ultrasonication technique.     

Influence of drug concentration on the diffusion parameters of caffeine

Background and Objectives:

In the fields of the pharmaceutical and cosmetic industries and in toxicology, the study of the skin penetration of molecules is very interesting. Various studies have considered the impact of different physicochemical drug characteristics, skin thickness, and formulations, on the transition from the surface of the skin to the underlying tissues or to the systemic circulation; however, the influence of drug concentration on the permeation flux of molecules has rarely been raised. Our study aims to discover the influence of caffeine concentration in a formulation on the percutaneous penetration from gels, as a result of different dose applications to polysulfate membrane and human skin.

Materials and Methods:

For this purpose, three identical base gels were used at 1, 3, and 5% of caffeine, to evaluate the effect of the concentration of caffeine on in vitro release through the synthetic membrane and ex vivo permeation through the human skin, using diffusion Franz^TM cells.

Results:

The diffusion through the epidermal tissue was significantly slower than through the synthetic membrane, which recorded an increase of flux with an increase in the concentration of caffeine. The skin permeation study showed that diffusion depended not only on the concentration, but also on the deposited amount of gel. Nevertheless, for the same amount of caffeine applied, the flux was more significant from the less concentrated gel.

Conclusion:

Among all the different concentrations of caffeine examined, 1% gel of caffeine applied at 5 mg / cm² showed the highest absorption characteristics across human skin.     

Development of diclofenac sodium-loaded alginate-PVP K 30 microbeads using central composite design

Background and the purpose of the study

Diclofenac sodium is a non-steroidal anti-inflammatory agent with a short biological half-life (1–2 hr) and requires multiple dosing. This research was carried out to develop and optimize diclofenac sodium loaded alginate-PVP K 30 microbeads to eliminate the need for multiple dosing and adverse effects.

Methods

Diclofenac sodium loaded alginate-PVP K 30 microbeads were prepared by ionotropic gelation. Particle size, drug release, swelling, FTIR and SEM analyses were performed.

Results

Optimized microbeads showed particle size of 0.589±0.054 to 0.620±0.067 mm, and drug entrapment efficiency of 97.88±2.86 to 98.60±3.55%. The in vitro drug release from microbeads was sustained over 10 hrs and followed controlled-release pattern. FTIR analysis indicated the possibility of intermolecular hydrogen bonding interactions, i.e., –OH…O=C in microbeads.

Conclusion

Microbeads for oral controlled delivery of diclofenac sodium were successfully developed by ionotropic gelation.     

The effect of sodium valproate on the biochemical parameters of reproductive function in male albino Wistar rats

Objective:

To assess the effects of sodium valproate on intratesticular testosterone and lactic dehydrogenase level in rats.

Methods:

Male Wistar rats (12 weeks old) were treated with sodium valproate and sacrificed at the end of the 2^nd, 4^th, 5^th, 7^th, 10^th and 15^th week, after the last exposure to sodium valproate. The testes were removed, weighed and processed for biochemical analysis.

Results:

The intratesticular testosterone level was significantly (P<0.001) reduced in 200 mg/kg and 400 mg/kg treated rats. The intratesticular lactate dehydrogenase (LDH) level was significantly (P<0.001) increased by valproate in a time dependent manner.

Conclusion:

Valproate causes reversible change in intratesticular testosterone and LDH level.     

Dose-effect study of domperidone as a galactagogue in preterm mothers with insufficient milk supply, and its transfer into milk

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Domperidone is an effective treatment for some mothers with insufficient milk supply.
• However, dose–effect data are not available, and the safety of domperidone use in both mother and infant has been questioned.

WHAT THIS STUDY ADDS

• Domperidone only increases milk production in about two-thirds of preterm mothers with insufficient milk supply.
• On average, the responders showed increasing levels of milk production with dose escalation from 30 mg to 60 mg daily.
• The amount of domperidone that transferred into breast milk was very low, and the risk to the breastfed infant is minimal.

AIMS

To investigate the possibility of a dose–response relationship for the use of domperidone in treating insufficient milk supply in mothers of preterm infants, and to quantify the exposure of the breastfed infant to domperidone.

METHODS

Six preterm mothers received domperidone (30 mg daily or 60 mg daily) in a double-blind, randomized, crossover trial. Milk production and serum prolactin were measured before and during the trial, and domperidone concentration in milk was measured during drug treatment.

RESULTS

For milk production, two of the mothers were ‘nonresponders’, whereas the other four were ‘responders’ and showed a significant increase in milk production from 8.7 ± 3.1 g h⁻¹ in the run-in phase (mean ± SEM), 23.6 ± 3.9 g h⁻¹ for the 30-mg dose (P = 0.0217) and 29.4 ± 6.6 g h⁻¹ for the 60-mg dose (P = 0.0047). In all participants, serum prolactin was significantly increased for both doses, but the response was not dose dependent. Median (interquartile range) domperidone concentrations in milk over a dose interval at steady-state were 0.28 µg l⁻¹ (0.24–0.43) and 0.49 µg l⁻¹ (0.33–0.72) for the 30-mg and 60-mg doses, respectively. The mean relative infant dose was 0.012% at 30 mg daily and 0.009% at 60 mg daily.

CONCLUSION

In one-third of mothers, domperidone did not increase milk production. In the remainder, milk production increased at both domperidone doses, and there was a trend for a dose–response relationship. The amount of domperidone that transfers into milk was extremely low, and infant exposure via breastfeeding was not considered to be significant.     

Calcium antagonistic activity of Bacopa monniera in guinea-pig trachea

Objective:

To demonstrate the calcium antagonistic property of ethanol extract of Bacopa monniera in guinea-pig trachea.

Materials and Methods:

The dose response curves of CaCl₂ (1 × 10^-5 to 1 × 10^-1 M) were constructed in the absence and presence of ethanol extract of Bacopa monniera (100, 500 and 700 μg/ml) or nifedipine (1 × 10^-6 M) in guinea-pig trachea in calcium free high K⁺-MOPS-PSS (3-(N-morpholino)-propanesulphonic acid physiological salt solution). The data was analyzed by ANOVA followed by least significant difference test or by Student''s ‘t’ test for unequal variance when appropriate. A probability of at least P < 0.05 was considered statistically significant.

Results:

The plant extract (500 and 700 μg/ml) significantly (P < 0.05) depressed and shifted the calcium concentration-response curves (1 × 10^-3- 1 × 10^-1 M) to rightward similar to that of nifedipine.

Conclusions:

Bacopa monniera extract exhibited calcium channel blocking activity in guinea-pig tracheal smooth muscles that may rationalize its relaxant action on guinea-pig trachea and its traditional use in respiratory disorders.KEY WORDS: Bacopa monniera, calcium channel antagonist, smooth muscle relaxation     

In vitro and In vivo characterization of the transdermal delivery of sertraline hydrochloride Films

Background and the purpose of the study

Sertraline hydrochloride is a selective serotonin reuptake inhibitor principally used in the treatment of major depressive disorder. To maintain the therapeutic plasma drug concentration of the drug for prolonged period, the transdermal drug delivery has been chosen as an alternative route of drug delivery. The pharmacokinetic properties of sertraline hydrochloride make it suitable for transdermal delivery. The purpose of the study was to investigate the effect of polymers and penetration enhancers on the transdermal delivery of the drug in order to improve its therapeutic efficacy.

Methods

In the preparation of films, Eudragit RL 100, Eudragit RS 100, hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose were used as polymers. The films were characterized for thickness, tensile strength, drug content, moisture uptake, moisture content, water vapor transmission rate and drug release. The films exhibiting higher rates of drug release were subjected to study the effect of oleic acid and propylene glycol as penetration enhancers on skin permeation of sertraline hydrochloride. In vivo and skin irritation studies were performed for the optimized film.

Results

Films containing Eudragit RL 100, Eudragit RL 100 and HPMC showed the highest drug release of 94.34% and 96.90% respectively in a period of 42 hrs. The release data fitted into kinetic equations, yielded zero-order and fickian mechanism of drug release. There was a two-fold increase in skin permeation of sertraline hydrochloride in the presence of penetration enhancers in the film. The physical evaluation indicated the formation of smooth, flexible and translucent films. No skin irritation occurred on rabbit skin and the infrared studies showed the compatibility of the drug with the formulation excipients. The in vivo study revealed a constant plasma concentration of drug for long periods and the films containing penetration enhancers had achieved adequate plasma levels of the drug.

Conclusions

The obtained results indicated the feasibility for transdermal delivery of sertraline hydrochloride using eudragit RL 100 and HPMC.     

Formulation and in vitro characterization of cefpodoxime proxetil gastroretentive microballoons

Background and the purpose of the study

The objective of the present work was to improve bioavailability of cepodoxime proxetil through gastroretentive microballoon formulation.

Methods

Microballoons of cefpodoxime proxetil were formulated by solvent evaporation and diffusion method employing hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) polymers and characterized for particle size, surface morphology, incorporation efficiency, floating behavior, in vitro drug release study and differential scanning calorimetry (DSC).

Results

The average particle size of formulated microballoons was in the range of 54.23±2.78–95.66±2.19µm. Incorporation efficiencies of over 83.77±0.85% were achieved for the optimized formulations. Most of formulations remained buoyant (having buoyancy percentage maximum of 81.36±1.96%) for more than 12 hrs indicating good floating behavior of microballoons. Higher values of correlation coefficients were obtained with Higuchi''s square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release.

Conclusion

Inferences drawn from in vitro studies suggest that microballoons may be potential delivery system for cefpodoxime proxetil with improvement in bioavailability in comparison to conventional dosage forms.     

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride

Background:

Propranolol hydrochloride, one of the most widely used β-blocker in the treatment of hypertension since 1960s, shows a number of serious and non-serious adverse events.

Objective:

Major objectives of this study were to extract the Canadian Adverse Drug Reaction Monitoring Program (CADRMP) database for possible toxic signal detection (SD) of propranolol hydrochloride, evaluate the frequency of the bradycardia associated with it in different stratified groups for a putative signal, and generate awareness in healthcare professionals regarding usefulness of SD.

Materials and Methods:

Appropriate statistical methods were used for adverse drug reaction (ADR) signal detection such as, proportional reporting ratio (PRR); reporting odds ratio (ROR); the Chi-square (χ²) statistic method; the 95% confidence interval (CI); the observed to expected ratio (O/E); and Du Mouchel method were used to calculate the possible signals. Significance of χ² and other calculated statistics, e.g., PRR and ROR, was based on a composite criterion of regulatory guidelines and not on any particular statistical level of significance.

Results:

Calculated statistics by different methods were compared with the regulatory criteria of a statistic value ≥4.0 for χ², and ≥3.0 for the rest for SD to be declared significant. The PRR statistic was found to be 2.5054; by the ROR method it was 2.5820; the χ² statistic was 3.2598, whereas the lower and upper limits of 95% CI of PRR were found to be 0.0778 and 1.9104, respectively, by the O/E ratio was found to be 2.3978, and PRR with the help of Du Mouchel was found to be 2.3979. Thus, the bradycardia–propranolol signals calculated in this study were not significant.

Conclusions:

The therapeutic class specific signal of bradycardia associated with propranolol hydrochloride was not found potent enough to cause bradycardia. However, since the calculated statistics were very high albeit not significant, the possibility of bradycardia–propranolol pairing should still be analyzed from larger databases.     

In-vitro red blood cell partitioning of doxycycline

Objective:

In-vitro red blood cell (RBC) partitioning of doxycycline was studied to determine whether doxycycline penetrates RBC and its concentration was assayed keeping in view its high lipophilicity.

Materials and Methods:

Standardization of doxycycline was performed in whole blood and plasma of cattle by microbiological assay using Bacillus subtillis ATCC 6633 as indicator organizm. Actual concentration of the drug was obtained by comparing zone inhibition with standard graph and the extent of partitioning was mathematically calculated.

Results:

The R² value of standard graph for doxycycline was 0.9934 and 0.9727 for plasma and whole blood, respectively. Overall, RBC partitioning of doxycycline was found to be 18.40 ± 1.70%.

Conclusions:

Overall RBC partitioning of doxycycline indicated low penetration into RBC. Plasma is the fluid suggested for pharmacokinetic evaluation of doxycycline.     

Chemical composition and vasorelaxant effect induced by the essential oil of Lippia alba (Mill.) N.E. Brown. (Verbenaceae) in rat mesenteric artery

Objectives:

To investigate the chemical composition and vasorelaxant effect of the essential oil of Lippia alba (EOLA) in rat mesenteric artery.

Material and Methods:

Chemical composition of EOLA was investigated by gas chromatography-mass spectrometry (GC/MS). Vasorelaxant effect was evaluated in vitro in rat superior mesenteric artery rings.

Results:

GC/MS analysis revealed the presence of 19 compounds, with geranial (48.58%) and neral (35.42%) being the major constituents. In intact rings precontracted with phenylephrine (Phe: 1 μM), EOLA (100-1000 μg/mL) induced relaxation, where the maximal effect (Emax) was 110.8 ± 10.8%. This effect was not modified after endothelium removal (Emax = 134.8 ± 16.5%), after tetraethylammonium (TEA) (Emax = 117.2 ± 4.96%), or in rings precontracted with KCl (80 mM) (Emax = 112.6 ± 6.70%). In addition, EOLA was able to inhibit the contraction caused by CaCl₂ and produced a small but significant (P<0.05) additional effect (from 70.5 ± 3.4 to 105.3 ± 13.5%, n = 5) on the maximal relaxation of nifedipine (NIF: 10 μM).

Conclusions:

The results demonstrated that EOLA induces endothelium-independent vasorelaxation, which appears to be caused, at least in part, by blocking Ca²⁺ influx through voltage-operated Ca²⁺ channels.KEY WORDS: Calcium channel, essential oil, Lippia alba, rat mesenteric artery, vasorelaxant effects     

Antioxidant activities of bark extract from mangroves, Bruguiera cylindrica (L.) Blume and Ceriops decandra Perr

Objectives:

The antioxidant activities of two Indian mangrove plants, Bruguiera cylindrica and Ceriops decandra, were investigated.

Materials and Methods:

Total phenolics and total flavonoid contents of the mangroves were determined using folin-ciocalteu reagent method and aluminium chloride method, respectively. Antioxidant capacity was assessed by the following methods: 1,1-diphenyl-2-picryl hydroxyl (DPPH.) quenching assay; 2,2’- azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS.⁺) cation decolorization test; scavenging capacity towards hydroxyl ion radicals (.OH); reductive capacity; and antihemolytic activity.

Results:

The mangroves yielded 233.3 ± 0.062 and 283.31 ± 0.04 mg gallic acid equivalent/g phenolic contents and 11.6 ± 0.12 and 15.1 ± 0.02 mg quercetin equivalent/g flavonoid contents. The methanol extracts of both mangroves exhibited high antiradical activity against DPPH., ABTS.⁺, and .OH radicals. The reductive capacity of the extracts increased with increasing concentration of samples. The extracts also inhibited H₂O₂ induced hemolysis in cow blood erythrocytes. The antioxidant activities were found stronger than that of the reference standard, butylated hydroxy toluene (BHT). The antioxidant activity of mangrove plants was correlated with total phenolics and flavonoid contents.

Conclusion:

Both plants can be considered as good sources of natural antioxidants for medicinal uses. Further studies are necessary to isolate active principles responsible for the overall antioxidant activity of the extracts.     

Development and Evaluation of a Novel Drug in Adhesive Transdermal System of Levodopa and Carbidopa

Purpose

Administration of levodopa along with carbidopa increases the availability of dopamine in the mid-brain, and this combination thereby is used in the treatment of parkinsonism. However, concomitant delivery of levodopa with carbidopa in oral therapy is limited by several issues and an alternative route would be advantageous. The current study assesses the feasibility of co-administration of levodopa and carbidopa through skin using a drug in adhesive transdermal system.

Methods

Drug in adhesive transdermal system containing levodopa (5 % w/w) and carbidopa (2.5 % w/w) (1 cm² area) was fabricated and assessed for in vitro drug release, ex vivo permeation, and in vivo pharmacokinetics in rat model.

Results

In vitro dissolution profiles indicated a biphasic pattern with an initial burst effect for both levodopa and carbidopa, although the drug release rate was relatively higher for carbidopa. Ex vivo permeation studies showed higher steady-state flux for levodopa (53.77?±?6.94 μg/cm²/h) and carbidopa (23.81?±?4.06 μg/cm²/h). In vivo studies revealed that the concomitant transdermal delivery of levodopa with carbidopa significantly changed the pharmacokinetic parameters of levodopa.

Conclusions

Given the promising results, this study concludes that the transdermal delivery route could be a feasible alternative to oral therapy for the successful delivery of levodopa in Parkinson’s disorder.     

An evaluation of the effects of nonselective and cardioselective ��-blockers on wound healing in Sprague Dawley rats

Objectives:

To investigate the effect of a nonselective β-blocker (propranolol) and cardioselective β-blocker (metoprolol) on wound healing in rats using incision and excision wound models and to compare the effect of these drugs on wound healing.

Materials and Methods:

Propranolol and metoprolol were given orally. Sprague Dawley rats of either sex were used. Incision and excision wound models were used to evaluate the wound-healing activity. Effects of metoprolol and propranolol on tensile strength, period of epithelialization, and hydroxyproline content were observed. Histological analysis was done to see collagen deposition and inflammatory infiltrate.

Statistical Analysis Used:

The data was subjected to analysis of variance (ANOVA) followed by Scheffe''s test. P < 0.05 was considered to be statistically significant. Statistical analysis was done using SPSS software version 15.0.

Results:

Administration of propranolol or metoprolol was shown to decrease tensile strength, delay wound contraction and re-epithelialization, increase inflammatory infiltrate, and reduce collagen density and hydroxyproline levels.

Conclusions:

The results suggest that nonselective and cardioselective β-blockers delay wound healing and these effects are mediated by β1-receptors.KEY WORDS: Excision wound model, incision wound model, metoprolol, propranolol     

Direct Technetium radiopharmaceuticals production using a 30MeV Cyclotron

Background and the purpose of the study

Technetium-99m is the major radionuclide used in the world and mainly is provided by fission product. However extensive research has been conducted on the use of accelerators for production of ^99mTc. This investigation reports the production of ^99mTc radioisotope using cyclotrons and the preparation, quality control and biodistribution studies of four major Tc-radiopharmaceuticals.

Methods

The high purity molybdenum natural target (130 mg/cm²) was irradiated in a Cyclone 30 accelerator using 160 µA of 25 MeV proton beam energy for 1000 µA-h. After dissolution, the technetium radionuclides were extracted using methyl ethyl ketone (MEK) followed by preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical samples.

Results

The results of quality controls and animal biodistribution studies showed successful production of Tc radionuclides (including ^99mTc) in the bombarded target and subsequent labelling of the kit with Tc.

Conclusion

The developed high power Mo target if constructed using enriched ¹⁰⁰Mo, could be a practical method for large-scale production of ^99mTc and promising as an alternative to fission product ⁹⁹Mo-^99mTc generators for local applications near cyclotron facilities.     

Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers

AIMS

To investigate the transfer of chloroquine and its major bioactive metabolite desethylchloroquine across the placenta and into breast milk.

METHODS

In Papua New Guinea, chloroquine (CQ; 25 mg base kg⁻¹) is recommended for prophylaxis of malaria during pregnancy, and at the Alexishafen Health Centre women are routinely prescribed CQ at the time of delivery. Fetal-cord and maternal serum samples were collected at delivery (n = 19) and milk samples were collected from day 3 to day 17–21 after delivery (n = 16). CQ and its primary active metabolite desethylchloroquine (DECQ) were quantified by high-performance liquid chromatography. For both CQ and DECQ cord/maternal ratios (C/M) were calculated to characterize placental transfer, and infant exposure via milk was estimated by standard methods.

RESULTS

The median (interquartile range) C/M was 1.1 (0.9, 1.6) for CQ and 1.2 (0.5, 1.8) for DECQ. The average concentration in milk over the time of sampling was 167 μg l⁻¹ (27, 340) for CQ and 54 μg l⁻¹ (22, 106) for DECQ. Estimated absolute and relative infant doses were 34 μg kg⁻¹ day⁻¹ (7, 50) and 15 μg kg⁻¹ day⁻¹ (4, 26), and 2.3% (0.5, 3.6) and 1.0% (0.4, 2.0) for CQ and DECQ (as CQ equivalents), respectively.

CONCLUSION

Infant exposure to CQ and DECQ during pregnancy will be similar to that in the maternal circulation, and dependent on maternal dose and frequency. The median CQ + DECQ relative infant dose of 3.2% (as CQ equivalents) was low, confirming that use of CQ during lactation is compatible with breastfeeding.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The literature on placental and milk transfer of chloroquine and its major bioactive metabolite desethylchloroquine is sparse and incomplete.

WHAT THIS STUDY ADDS

• We have provided data on the transplacental transfer of chloroquine and desethylchloroquine in Melanesian women (n = 19), measured transfer of these drugs into breast milk (n = 16) and estimated absolute and relative infant doses for the breastfed infant.
• The data for desethylchloroquine are novel.
• In all three areas we have significantly increased both quantity and quality of the available database.

     

Evaluation of an oral insulin formulation in normal and diabetic rats

Aim:

As injection is not an ideal means for insulin delivery, various attempts have been made to administer insulin orally until now. The development of an oral dosage form of insulin would help diabetic patients and make the treatment more convenient. The aim of the present study is to evaluate the effectiveness of an oral insulin formulation containing polar and non-polar ingredients.

Materials and Methods:

New excipient for oral insulin administration in normal and diabetic rats was evaluated by measuring blood glucose concentrations in two groups (10 rats each) of normal and streptozotocin-induced diabetic rats. Oral insulin was administrated and blood glucose was measured by glucometer at 0, 1, 2, 3 and 4 h post-feeding. The data was compared by Student''s t test.

Results:

Oral insulin formulation significantly (P<0.05) reduced blood glucose from 100 mg/dl to 33.73 mg/dl and 451.66 mg/dl to 200.83 mg/dl at 4 h in normal and diabetic rats, respectively.

Conclusion:

The novel excipient used could protect insulin from gastric and pancreatic enzymes and reduce blood glucose concentration in both healthy and diabetic rats suggesting that oral delivery of insulin is feasible in a near future.KEY WORDS: Blood glucose, normal and diabetic rats, oral insulin