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The objective of the present study was to evaluate the fate of three chemical sunscreens, isoamyl p-methoxycinnamate (IPMC), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and bis-ethylhexylphenol methoxyphenyl triazine (BEMT), topically applied to mammalian skin from a skin barrier mimetic oil-in-water formulation. High Performance Liquid Chromatography (HPLC) methods were developed for the analysis of each molecule and validated. Franz cell permeation studies were conducted following application of finite doses of the formulations to excised porcine skin. A vehicle formulation containing no sunscreens was evaluated as a control. Permeation studies were conducted for 12 h after which full mass balance studies were carried out. Analysis of individual UV sunscreens was achieved with HPLC following application of the formulation to the skin with no interference from the vehicle components. No skin permeation of any of the chemical sunscreens was evident after 12 h. While sunscreens were detected in up to 12 tape strips taken from the SC, 87% or more of the applied doses recovered in the first 5 tape strips. When corrected for the amount of protein removed per tape strip this corresponded to a penetration depth in porcine stratum corneum of ∼1.7 μm. Mass balance studies indicated total recovery values were within accepted guidelines for cosmetic formulations. Overall, only superficial penetration into the SC was observed for each compound. These findings are consistent with the physicochemical properties of the selected UV absorbing molecules and their formulation into an ordered biomimetic barrier formulation thus support their intended use in topical consumer formulations designed to protect from UV exposure. To our knowledge this is the first report of depth profiling of chemical sunscreens in the SC that combines tape stripping and protein determination following in vitro Franz cell studies.

Anthramycin (ANT) is a member of the pyrolobenzodiazepine family and is a potent cytotoxic agent. Previously, we reported the topical delivery of ANT from a range of solvents that may also act as skin penetration enhancers (SPEs). The skin penetration and uptake was monitored for simple solutions of ANT in propylene glycol (PG), dipropylene glycol (DiPG), Transcutol P (TC), isopropyl myristate (IPM), propylene glycol monocaprylate (PGMC) and propylene glycol monolaurate (PGML). The amounts of PG, DiPG and TC that were taken up by, and that penetrated the skin were also measured, with a clear dependence of ANT penetration on the rate and extent of PG and TC permeation. The present work investigates ANT skin delivery from a range of binary and ternary systems to determine any potential improvement in skin uptake compared with earlier results for the neat solvents. Following miscibility and stability studies a total of eight formulations were taken forward for evaluation in human skin in vitro. Binary systems of PG and water did not result in any skin permeation of ANT. Combining PG with either PGMC or PGML did promote skin penetration of ANT but no significant improvement was evident compared with PG alone. More complex ternary systems based on PG, DiPG, PGMC, PGML and water also did not show significant improvements on ANT permeation, compared with single solvents. Total skin penetration and retention of ANT ranged from 1 to 6% across all formulations studied. Where ANT was delivered to the receptor phase there were also high amounts of PG permeation with >50% and ~35% PG present for the binary systems and ternary vehicles respectively. These findings along with our previous paper confirm PG as a suitable solvent / SPE for ANT either alone or in combination with PGML or PGMC. The results also underline the necessity for empirical testing to determine whether or not a vehicle is acting as a SPE for a specific active in a topical formulation.

Anthramycin (ANT) was the first pyrrolobenzodiazepine (PBD) molecule to be isolated, and is a potent cytotoxic agent. Although the PBD family has been investigated for use in systemic chemotherapy, their application in the management of actinic keratoses (AK) or skin cancer has not been investigated to date. In the present work, anthramycin (ANT) was selected as a model PBD compound, and the skin penetration of the molecule was investigated using conventional Franz diffusion cells. Finite dose permeation studies of ANT were performed using propylene glycol (PG), 1,3-butanediol (BD), dipropylene glycol (DiPG), Transcutol P® (TC), propylene glycol monocaprylate (PGMC), propylene glycol monolaurate (PGML) and isopropyl myristate (IPM). The skin penetration of BD, DiPG, PG and TC was also measured. Penetration of ANT through human skin was evident for TC, PG and PGML with the active appearing to "track" the permeation of the vehicle in the case of TC and PG. Deposition of ANT in skin could be correlated with skin retention of the vehicle in the case of IPM, PGMC and PGML. These preliminary findings confirm the ability of ANT to penetrate human skin and, given the potency of the molecule, suggest that further investigation is justified. Additionally, the findings emphasise the critical importance of understanding the fate of the excipient for the rational design of topical formulations.

In this present study an attempt has been made to evaluate glyceryl monostearate (GMS) as a rate retarding material to sustain the release ciprofloxacin hydrochloride from the matrix tablet. The solubility of ciprofloxacin hydrochloride was studied. The physical parameters of the prepared tablets were also evaluated. Release kinetics of ciprofloxacin hydrochloride from this sustained release matrix was studied in 0.1 N HCl using United States Pharmacopoeia type-II dissolution apparatus (paddle method). The effect of polymer load, drug load, hydroxylpropylmethylcellulose to compensate glyceryl monostearate (GMS) and different release modifiers were examined. It was observed that the release rate of drug was retarded with the increasing concentration of GMS. The release data were treated in different fashion to identify the release mechanism and it was revealed with few exception that, when GMS is used as single polymer, release of active drug from the prepared matrix tablet appeared to follow the first order kinetics and showed the tendency to follow Korsmeyer model when HPMC 15 cps was used along with GMS. Using release enhancers the release pattern were fitted to first order kinetics. From the f 2 values it can be concluded that the release pattern of P-2, D-1, H-2 and H-3 are similar to P-1, whereas the formula of P-1, D-2 and H-1 were same. MDT values were found to be increased with the increasing amount of polymer (GMS). Key words: Glyceryl monostearate; ciprofloxacin HCl; sustained release matrix; dissolution studies. DOI: 10.3329/dujps.v8i1.5340 Dhaka Univ. J. Pharm. Sci. 8(1): 81-88, 2009 (June)

The objective of this study was to develop a simple, efficient, precise and accurate reverse-phase HPLC method for the simultaneous determination of metformin in combination with gliclazide in newly formulated tablets. Chromatographic determination was performed on a reversed phase C18 column (2.6 mm x 250 mm; 5 μm particle size) using a mixture of buffer (1 ml of orthophosphoric acid with 1 ml triethylamine upto 1000 ml with HPLC grade water) and methanol at the ratio of 60:40 as mobile phase at a flow rate of 1ml/min. The UV detection was set at 230 nm. Under the developed conditions, good separation of the analytes was achieved. The calibration curves were linear with coefficient correlation between 0.998 to 1.0 for both drugs over a concentration range of 1 to 50 μg/ml for metformin hydrochloride and 0.16 to 8 μg/ml for gliclazide. The method was also validated in terms of precision (RSD = 0.06 to 3.22%) and accuracy (percent deviation = 0.049 to 2.602%). The proposed method was applied for the analysis of these analytes in newly formulated tablets and potencies were found to be 99.41±0.24% for metformin hydrochloride and 99.77±0.37% for gliclazide which were acceptable. Key words: HPLC; metformin hydrochloride; gliclazide; combination dosage form; tablet. DOI: http://dx.doi.org/10.3329/dujps.v9i2.7884 Dhaka Univ. J. Pharm. Sci. 9(2): 83-89, 2010 (December)

Aceclofenac loaded agarose beads were prepared by ionotropic gelation method and drug release profile, swelling index (SI %) and entrapping efficiency (EE %) of aceclofenac were investigated. The drug was dissolved in melted 4 % agar solution in different ratios. Beads were prepared by dropping the hot aqueous solution into a beaker of different percentages of chilled CaCl2 solution followed by filtering the solution and drying at room temperature. The entrapment efficiency was 100±5 %. The swelling index was found to be highest (18.22 % in 4 hours) for beads containing aceclofenac-agar (1:2) in 4 % electrolyte solutions and the swelling property was decreased with increasing electrolyte concentration. In vitro dissolution of beads was carried out in USP apparatus-II (paddle method) at 75 rpm. The drug release was measured by using UV-Spectrophotometer at λmax of 268 nm for acid media and 274 nm for buffer media. The dissolution data were treated with zero order, first order and Higuchi model. Half of the formulations were fitted to Higuchi model and rest half to first order model. Finally it can be concluded that with the increasing polymer (agar) concentration, the release rate of aceclofenac was decreased and swelling index was increased and with the increasing electrolyte concentration, the release rate was increased and swelling index was decreased. Key Words: Aceclofenac, Agarose bead, Electrolyte, Ionotropic Gelation method.  doi:10.3329/sjps.v1i1.1780 S. J. Pharm. Sci. 1(1&2):10-17

The present study was carried out to develop biodegradable intrascleral implants of Dexamethasone Sodium Phosphate and to evaluate the release pattern of the drug from the prepared implants. Intrascleral implants were prepared by using biodegradable polymer L-PLA (m.wt. 61,200 Da). Sodium chloride (NaCl), gelatin and glycerol monostearate (GMS) were used in various formulations to observe the effects of these additives on the release of Dexamethasone Sodium Phosphate from the prepared L-PLA based intrascleral implants. Five different formulations were prepared for this study and were coded as FD-1 (10%drug+L-PLA), FD-2 (20%drug+L-PLA), FD-3 (10%drug+L-PLA+5%NaCl), FD-4 (10%drug+L-PLA +5%Gelatin) and FD-5 (10%drug+L-PLA+10% GMS). Discs were prepared and made into appropriate shape before submerging into the buffer solution of pH 7.4 in different vials. The in vitro release profile of Dexamethasone Sodium Phosphate from the implants showed a biphasic release pattern with an initial burst followed by a diffusive phase. It was observed that FD-1 and FD-2 showed 19.63% and 29.87% release on the first day and 24.22% and 38.5% release respectively at day 30. The drug loading of FD-1 and FD-2 was 10% and 20% respectively. Among FD-3, FD-4 and FD-5; FD-3 showed highest release (32.1%) at day 30 in which 5% NaCl was used. FD-4 showed 27.45% release at day 30 where gelatin, a hydrophilic agent was used and FD-5 containing GMS, a lipid material, was found to be most retarding (19.22% at day 30). The results of the dissolution study provide an idea that L-PLA may be successfully used for the preparation of biodegradable intrascleral implant of Dexamethasone Sodium Phosphate. Key words: Dexamethasone Sodium Phosphate; Bioidegradable polymer; Intrascleral implants. DOI: 10.3329/sjps.v2i1.5817Stamford Journal of Pharmaceutical Sciences Vol.2(1) 2009: 56-60

In the present study Ciprofloxacin HCl sustained release matrix tablet was prepared by utilizing different grades of hydroxypropyl methylcellulose (HPMC) polymers such as Methocel K4M CR, Methocel K4M Premium & Methocel K15M CR by direct compression method. Different amount of Methocel K15M CR was used to develop matrix builder in the three proposed formulations (F1-F3) for the study of release rate retardant effect at 5%, 6%, and 7% of total weight of tablet matrix respectively. The dissolution study of Methocel K15M CR based tablet matrices of those proposed formulations were carried out in the simulated gastric medium (pH 1.3) for 8 hours using USP dissolution apparatus II. Similarly Methocel K4M premium was used to develop matrix builder in another three proposed formulations (F4-F6). It was found that formulations F-4 (15%), F-5 (17%) and F-6 (18.3%) met the desired release rate of Ciprofloxacin HCl for 8hrs period. The release kinetics of formulation F-4, F-5 and F-6 followed Higuchi kinetic order. Again Methocel K4M premium was used for another three proposed formulations (F7-F9). It was found that formulations F-7 (6.7%), F-8 (12.3%) and F-9 (15.6%) met the desired release rate of Ciprofloxacin HCl for 8hrs period. The release kinetics of formulation F-7, F-8 and F-9 followed Higuchi kinetic order. Among these three polymers, Methocel K4M Premium showed better release retardant effect than Methocel K4M CR and Methocel K15M CR. Key Words: Ciprofloxacin HCl; Direct compression; Controlled release; Methocel K15M CR; Methocel K4M CR; Methocel K4M premium.DOI: 10.3329/sjps.v2i1.5814Stamford Journal of Pharmaceutical Sciences Vol.2(1) 2009: 37-43

In the present study sustained release diclofenac sodium matrix tablets were prepared using Kollidon SR polymer. Hydroxypropyl methylcellulose (HPMC 15 cps) and poly ethylene glycol (PEG-600) polymers respectively were used in formulating tablets prepared by direct compression and wet granulation methods. The polymers were used to explore the release pattern of the drug into the dissolution media. The tablets were also prepared in various shapes (caplet oval, round oval and flat oval). A comparatively higher release rate of drug was obtained from the polymer HPMC 15 cps at 10% concentration for directly compressed matrix tablet than those containing 20% of HPMC after a definite period of time. In wet granulation process, 10% PEG-600 containing tablets showed a better release than those containing 20% PEG. The drug release was also found to be sustained in case of wet granulation method than that of the direct compression method. Again the caplet shaped tablets in case of direct compression method showed better release rate of drug than those of the round oval and flat oval shaped tablets. Thus the result of this study shows that the proper selection of the percentage of polymer and the suitable shape of tablet and proper manufacturing method can provide a greater opportunity in designing sustained release dosage forms. Key words: Matrix tablet; release pattern; direct compression; wet granulation; PEG 600; Kollidon SR. DOI: 10.3329/sjps.v2i2.5828 Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 76-80

In this work zinc sulfate, ferrous sulfate and ascorbic acid was formulated on the same pellet by combination pelletization technique and their and in vitro dissolution studies were performed by using United States Pharmacopoeia (USP) apparatus type II. In addition, effect of different types of polymers, formulation variables and variations in coating composition on the release of drug were studied. The desired release profile for ferrous sulfate was 35% for 1st hour, 45-75% for 2nd hour and 60-85% for third hour and not less than 85% for 4th hour. The release rate controlling polymer used was various concentrations of Methoccel K15M CR with different concentrations of Microcrystalline cellulose (Avicel PH 101). The maximum release percentage of Ferrous Sulphate was obtained from 2.5 % of Methocel K15M CR and 30 % Avicel PH 101 containing pellets (F-4) and it was 92.32%. And the minimum release percentage of Ferrous Sulphate was obtained from 10 % of Methocel K15M CR and 35.7% Avicel PH 101 containing pellets (F-1) and it was 86.36%. The release profile from other formulations containing 35.4% Methocel K 15M CR & 7.5% Avicel (F-2) and 32% Methocel K 15M CR & 4% Avicel (F-3) were also within desired range. The effect of Eudragit coating (enteric) and the presence of PEG and HPMC in the film coating composition on the drug release were also investigated. Hydrophobic matrix pellets prepared using lower concentrations of Methocel K15M CR were found to be best suited for modulating the delivery of the ferrous sulphate from the combination. Key words: Non Pariel Seeds (NPS); Pan Coater; Ascorbic acid; Methocel K15M CR; Pelletization; PEG; Avicel PH 101; Xanthan gum.DOI: 10.3329/sjps.v2i2.5824Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 53-58

Hydrophilic polymers are widely used to prepare sustained release matrix tablets. These polymers showed their sustained action by forming a barrier of thick gel layer around the matrix. Here swelling of the polymer and erosion of matrix plays a major role to control the release of the drug. In this present study the swelling and erosion properties of some hydrophilic polymers were correlated to their sustaining and rate controlling behavior. Matrix tablets containing hydroxypropyl methylcellulose (HPMC K100cps), carboxymethyl cellulose (CMC 50,000 cps) and methocel K15M CR polymers were prepared. The powder mixture was evaluated for their flow properties and the prepared tablets for their physical parameters. Swelling and erosion index of the tablets were carried out in pH 6.8 phosphate buffer and dissolution in 0.1N HCl (2 hours) followed by pH 6.8 phosphate buffer (8 hours) using USP apparatus II (paddle method) at 50 r.p.m. HPMC K100 cps was found to be not as rate retarding as the other two. From the all results it was observed that F-6 (containing 43.243% methocel K15M CR) showed highest swelling and erosion index (740.589% and 12.017% respectively), slowest release rate (24.491% at 8 hours) and highest MDT value (55.401 hours). Finally it can be concluded that increasing the polymer concentration or polymer's viscosity grade, swelling and erosion index increases, release rate decreases and MDT value increases. Key words: Aceclofenac; Matrix tablets; HPMC; CMC; Physical parameters; Release kinetics. DOI: 10.3329/bjsir.v45i2.5712Bangladesh J. Sci. Ind. Res. 45(2), 141-150, 2010