methylcellulose and isopropyl-myristate

Drotaverine hydrochloride (DRT) is used to treat gastrointestinal spasms accompanied with diarrhoea. Hence, the drug suffers from brief residence in the highly moving intestine during diarrhoea which leads to poor bioavailability and frequent dosing.. This study aimed to extend DRT residence in the stomach.. Calcium alginate floating beads were prepared using sodium alginate, isopropylmyristate (oil), and Gelucire® 43/01 (lipid) adopting emulsion gelation technique. The beads were evaluated for their floating ability, DRT entrapment efficiency and in-vitro release. Gelucire® 43/01 /oil-based beads of the selected formula were coated using ethylcellulose and different plasticizers as polyethylene glycol 400 and triethyl citrate to retard the drug release. The coated beads were re-characterized. Finally, the best formulae were investigated for their in-vivo floating ability in dogs besides their delivery to the systemic circulation compared to drug powder in human volunteers.. Incorporation of Gelucire® 43/01 to oil-based beads enhanced the in-vitro performance of the beads. Coated beads prepared using drug:sodium alginate ratio of 1:3 (w/w), 20% (w/v) isopropylmyristate, 20% (w/v) Gelucire® 43/01 showed promising in-vitro performance. The beads floated for 12 h in the dogs' stomach and produced three-fold increase of the total amount of DRT absorbed within 24 h compared to that of DRT powder.. Gelucire® 43/01 /isopropylmyristate-based calcium alginate floating beads coated with ethylcellulose using either PEG 400 or TEC as plasticizers proved to be a successful dosage form in extending DRT release.

Topics: Adult; Alginates; Animals; Diarrhea; Dogs; Drug Delivery Systems; Emulsions; Glucuronic Acid; Hexuronic Acids; Humans; Liposomes; Methylcellulose; Myristates; Papaverine; Parasympatholytics; Pharmaceutical Preparations; Triglycerides

The objective of the present study was to formulate an insulin emulgel, selection of an optimize formulation through in vitro drug release kinetics and finally evaluate its hypoglycemic activity in animal model. Insulin emulgel was prepared using emu oil as penetration enhancer with the combination of carbomer or hydroxypropyl methylcellulose (HPMC) as gelling agent and polysorbate 80 as emulsifier. The response of gelling agent type (carbomer or HPMC) and concentration of other two variables penetration enhancer and emulsifier were studied using 2(3)factorial design during in vitro drug release through excised rat skin. Biological activity of emulgel formulation was also investigated using Albino rabbits alone and in combination with iontophoresis. The in vivo efficacy of insulin emulgel was assessed by measuring the blood glucose level at start of the experiment and after every 15 minutes interval for 120 minutes. Total eight formulations were studied. F4 formulation showed maximum insulin permeation flux (4.88 ± 0.09 μg/cm(2)/hour) through excised rat skin. Insulin permeation from these formulations was found to follow the Korsmeyer-Peppas model (r(2) =0.975 to 0.998) during 24 hour with non-Fickian mechanism. Formulation F4 was further investigated in Albino rabbits. For the first group (treated with insulin emulgel alone) the blood glucose level decreased from initial value 250±10mg/dl to 185±7mg/dl at 120 minutes and for the second group (treated with insulin emulgel plus iontophoresis) the blood glucose level decreased to 125±5mg/dl in 120 minutes (P<0.05). It was observed that absorption of insulin through transdermal emulgel was greater in combination with iontophoresis to decrease blood glucose level. On the basis of this study, it has been shown that application of insulin emulgel iontophoretically can be used as alternative (acceptable & painless) to injectable insulin subject to further studies on large animals.

Topics: Acrylic Resins; Administration, Cutaneous; Animals; Blood Glucose; Chemistry, Pharmaceutical; Drug Carriers; Emulsifying Agents; Gels; Hypoglycemic Agents; Hypromellose Derivatives; Insulin; Iontophoresis; Kinetics; Methylcellulose; Models, Biological; Myristates; Oils; Permeability; Polysorbates; Rabbits; Rats; Skin; Skin Absorption; Solubility; Technology, Pharmaceutical

The objective was to investigate the suitable polymeric films for the development of diltiazem hydrochloride (diltiazem HCl) transdermal drug delivery systems. Hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) were used as hydrophilic and hydrophobic film formers, respectively. Effects of HPMC/EC ratios and plasticizers on mechanical properties of free films were studied. Effects of HPMC/EC ratios on moisture uptake, in vitro release and permeation through pig ear skin of diltiazem HCl films were evaluated. Influence of enhancers including isopropyl myristate (IPM), isopropyl palmitate (IPP), N-methyl-2-pyrrolidone, oleic acid, polyethylene glycol 400, propylene glycol, and Tween80 on permeation was evaluated. It was found that addition of EC into HPMC film produced lower ultimate tensile strength, percent elongation at break and Young's modulus, however, addition of EC up to 60% resulted in too hard film. Plasticization with dibutyl phthalate (DBP) produced higher strength but lower elongation as compared to triethyl citrate. The moisture uptake and initial release rates (0-1 h) of diltiazem HCl films decreased with increasing the EC ratio. Diltiazem HCl films (10:0, 8:2 and 6:4 HPMC/EC) were studied for permeation because of the higher release rate. The 10:0 and 8:2 HPMC/EC films showed the comparable permeation-time profiles, and had higher flux values and shorter lag time as compared to 6:4 HPMC/EC film. Addition of IPM, IPP or Tween80 could enhance the fluxes for approx. three times while Tween80 also shorten the lag time. In conclusion, the film composed of 8:2 HPMC/EC, 30% DBP and 10% IPM, IPP or Tween80 loaded with 25% diltiazem HCl should be selected for manufacturing transdermal patch by using a suitable adhesive layer and backing membrane. Further in vitro permeation and in vivo performance studies are required.

Topics: Administration, Cutaneous; Animals; Calcium Channel Blockers; Cellulose; Chemistry, Pharmaceutical; Citrates; Delayed-Action Preparations; Dibutyl Phthalate; Diffusion; Diffusion Chambers, Culture; Diltiazem; Dosage Forms; Drug Carriers; Drug Compounding; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Chemical; Myristates; Palmitates; Permeability; Plasticizers; Polysorbates; Skin; Skin Absorption; Solubility; Swine; Technology, Pharmaceutical; Tensile Strength; Water

To prepare the alpha-asarone reservoir patch and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug's permeation rate.. The alpha-asarone reservoir patch was prepared using 1% hydroxypropyl methylcellulose (HPMC) of ethanol solution as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and several permeation enhancers were evaluated. High performance liquid chromatorgraphy (HPLC) was used to determine alpha-asarone's content and permeation rate.. The release mechanisms of alpha K-asarone patch in vitro coincided with zero-order kinetic. 30% ethanol cooperates with 1% Isopropyl Myristate (IPM) have the best effect on permeation of the patch. The permeation rate reaches (20.67 +/- 1.33) microg x cm(-2) h(-1).. Ethanol combined with IPM is good permeation enhancer, which facilitated the permeation of alpha K-asarone to fit the clinical requirements. However, the further studies of the skin's stimulation and bioavailability are needed.

Topics: Acorus; Administration, Cutaneous; Allylbenzene Derivatives; Anisoles; Delayed-Action Preparations; Ethanol; Humans; Hypromellose Derivatives; In Vitro Techniques; Methylcellulose; Myristates; Plants, Medicinal; Polyvinyls; Skin; Skin Absorption