Formulation Development of Itraconazole Nanocrystals

The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and nontoxic for a prolonged period. Various attempts have been made to develop gastroretentive delivery systems such as high density system, swelling, floating system. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application. Background of the research: Diltiazem HCL (DTZ), has short biological half life of 3-4 h, requires rather high frequency of administration. Due to repeated administration there may be chances of patient incompliance and toxicity problems. Objective: The objective of study was to develop sustained release alginate beads of DTZ for reduction in dosing frequency, high bioavailability and better patient compliance. Methodology: Five formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared. Alginate beads were prepared by ionotropic external gelation technique using CaCl2 as cross linking agent. Prepared beads were evaluated for % yield, entrapment efficiency, swelling index in 0.1N HCL, drug release study and SEM analysis. In order to improve %EE and drug release, LMP and sunflower oil were used as copolymers along with sodium alginate.

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Novel Formulation Development and Evaluation of Nanoparticles Based in Situ Gelling System for The Ophthalmic Delivery of Ciprofloxacin Hydrochloride

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v5i4.8880 ◽

2015 ◽

Vol 5 (4) ◽

Author(s):

Kranti Singh ◽

Surajpal Verma ◽

Shyam Prasad ◽

Indu Bala

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Drug Loading ◽

In Vitro Release ◽

Formulation Development ◽

Ciprofloxacin Hydrochloride ◽

Potential Value ◽

The Mean ◽

In Situ Gelling

Ciprofloxacin hydrochloride loaded Eudragit RS100 nanoparticles were prepared by using w/o/w emulsification (multiple emulsification) solvent evaporation followed by drying of nanoparticles at 50°C. The nanoparticles were further incorporated into the pH-triggered in situ gel forming system which was prepared using Carbopol 940 in combination with HPMC as viscosifying agent. The developed nanoparticles was evaluated for particle size, zeta potential value and loading efficiency; nanoparticle incorporated in situ gelling system was evaluated for pH, clarity, gelling strength, rheological studies, in-vitro release studies and ex-vivo precorneal permeation studies. The nanopaticle showed the mean particle size varying between 263.5nm - 325.9 nm with the mean zeta potential value of -5.91 mV to -8.13 mV and drug loading capacity varied individually between 72.50% to 98.70% w/w. The formulation was clear with no suspended particles, showed good gelling properties. The gelling was quick and remained for longer time period. The developed formulation was therapeutically efficacious, stable and non-irritant. It provided the sustained release of drug over a period of 8-10 hours.

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A Rapid Formulation Development and Clinical Testing Program to Evaluate the Pharmacokinetics of a Novel Enabled Formulation of Compound-X

10.26226/morressier.57d6b2bdd462b8028d88d288 ◽

2016 ◽

Author(s):

John McDermott

Keyword(s):

Clinical Testing ◽

Formulation Development ◽

Testing Program

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QbD Approach to Formulation Development for a Suspension Based Soft Gelatin Dosage Form

10.26226/morressier.57d6b2bbd462b8028d88d20b ◽

2016 ◽

Author(s):

Saujanya Gosangari

Keyword(s):

Dosage Form ◽

Formulation Development

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Mechanisms of Drug Solubilization by Polar Lipids in Biorelevant Media

10.26434/chemrxiv.12649145.v1 ◽

2020 ◽

Author(s):

Vladimir Katev ◽

Zahari Vinarov ◽

Slavka S. Tcholakova

Keyword(s):

Chain Length ◽

Acyl Chain ◽

Polar Lipids ◽

Superior Performance ◽

Head Group ◽

Formulation Development ◽

Biorelevant Media ◽

Drug Solubilization ◽

Colloidal Aggregates ◽

Class 1

Despite the widespread use of lipid excipients in both academic research and oral formulation development, rational selection guidelines are still missing. In the current study, we aimed to establish a link between the molecular structure of commonly used polar lipids and drug solubilization in biorelevant media. We studied the effect of 26 polar lipids of the fatty acid, phospholipid or monoglyceride type on the solubilization of fenofibrate in a two-stage in vitro GI tract model. The main trends were checked also with progesterone and danazol. Based on their fenofibrate solubilization efficiency, the polar lipids can be grouped in 3 main classes. Class 1 substances (n = 5) provide biggest enhancement of drug solubilization (>10-fold) and are composed only by unsaturated compounds. Class 2 materials (n = 10) have an intermediate effect (3-10 fold increase) and are composed primarily (80 %) of saturated compounds. Class 3 materials (n = 11) have very low or no effect on drug solubilization and are entirely composed of saturated compounds. The observed behaviour of the polar lipids was rationalized by using two classical physicochemical parameters: the acyl chain phase transition temperature (Tm) and the critical micellar concentration (CMC). Hence, the superior performance of class 1 polar lipids was explained by the double bonds in their acyl chains, which: (1) significantly decrease Tm, allowing these C18 lipids to form colloidal aggregates and (2) prevent tight packing of the molecules in the aggregates, resulting in bigger volume available for drug solubilization. Long-chain (C18) saturated polar lipids had no significant effect on drug solubilization because their Tm was much higher than the temperature of the experiment (T = 37 C) and, therefore, their association in colloidal aggregates was limited. On the other end of the spectrum, the short chain octanoic acid manifested a high CMC (50 mM), which had to be exceeded in order to enhance drug solubilization. When these two parameters were satisfied (C > CMC, Tm < Texp), the increase of the polar lipid chain length increased the drug solubilization capacity (similarly to classical surfactants), due to the decreased CMC and bigger volume available for solubilization. The hydrophilic head group also has a dramatic impact on the drug solubilization enhancement, with polar lipids performance decreasing in the order: choline phospholipids > monoglycerides > fatty acids. As both the acyl chain length and the head group type are structural features of the polar lipids, and not of the solubilized drugs, the impact of Tm and CMC on solubilization by polar lipids should hold true for a wide variety of hydrophobic molecules. The obtained mechanistic insights can guide rational drug formulation development and thus support modern drug discovery pipelines.

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Mechanisms of Drug Solubilization by Polar Lipids in Biorelevant Media

10.26434/chemrxiv.12649145 ◽

2020 ◽

Author(s):

Vladimir Katev ◽

Zahari Vinarov ◽

Slavka S. Tcholakova

Keyword(s):

Chain Length ◽

Acyl Chain ◽

Polar Lipids ◽

Superior Performance ◽

Head Group ◽

Formulation Development ◽

Biorelevant Media ◽

Drug Solubilization ◽

Colloidal Aggregates ◽

Class 1

Despite the widespread use of lipid excipients in both academic research and oral formulation development, rational selection guidelines are still missing. In the current study, we aimed to establish a link between the molecular structure of commonly used polar lipids and drug solubilization in biorelevant media. We studied the effect of 26 polar lipids of the fatty acid, phospholipid or monoglyceride type on the solubilization of fenofibrate in a two-stage in vitro GI tract model. The main trends were checked also with progesterone and danazol. Based on their fenofibrate solubilization efficiency, the polar lipids can be grouped in 3 main classes. Class 1 substances (n = 5) provide biggest enhancement of drug solubilization (>10-fold) and are composed only by unsaturated compounds. Class 2 materials (n = 10) have an intermediate effect (3-10 fold increase) and are composed primarily (80 %) of saturated compounds. Class 3 materials (n = 11) have very low or no effect on drug solubilization and are entirely composed of saturated compounds. The observed behaviour of the polar lipids was rationalized by using two classical physicochemical parameters: the acyl chain phase transition temperature (Tm) and the critical micellar concentration (CMC). Hence, the superior performance of class 1 polar lipids was explained by the double bonds in their acyl chains, which: (1) significantly decrease Tm, allowing these C18 lipids to form colloidal aggregates and (2) prevent tight packing of the molecules in the aggregates, resulting in bigger volume available for drug solubilization. Long-chain (C18) saturated polar lipids had no significant effect on drug solubilization because their Tm was much higher than the temperature of the experiment (T = 37 C) and, therefore, their association in colloidal aggregates was limited. On the other end of the spectrum, the short chain octanoic acid manifested a high CMC (50 mM), which had to be exceeded in order to enhance drug solubilization. When these two parameters were satisfied (C > CMC, Tm < Texp), the increase of the polar lipid chain length increased the drug solubilization capacity (similarly to classical surfactants), due to the decreased CMC and bigger volume available for solubilization. The hydrophilic head group also has a dramatic impact on the drug solubilization enhancement, with polar lipids performance decreasing in the order: choline phospholipids > monoglycerides > fatty acids. As both the acyl chain length and the head group type are structural features of the polar lipids, and not of the solubilized drugs, the impact of Tm and CMC on solubilization by polar lipids should hold true for a wide variety of hydrophobic molecules. The obtained mechanistic insights can guide rational drug formulation development and thus support modern drug discovery pipelines.

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Formulation and Evaluation of Immediate Release Bilayer Tablets of Telmisartan and Hydrochlorothiazide

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2011.4.3.6 ◽

2011 ◽

Vol 4 (3) ◽

pp. 1477-1483

Author(s):

Natarajan R ◽

N Patel ◽

Rajendran N N ◽

M Rangapriya

Keyword(s):

Antihypertensive Drugs ◽

In Vitro Release ◽

Immediate Release ◽

Wet Granulation ◽

Physical Parameters ◽

Dissolution Profile ◽

Formulation Development ◽

Sodium Starch Glycolate ◽

Bilayer Tablets

The main goal of this study was to develop a stable formulation of antihypertensive drugs telmisartan and hydrochlorothiazide as an immediate-release bilayer tablet and to evaluate the dissolution profile in comparison with a reference product. The formulation development work was initiated with wet granulation. Telmisartan was converted to its sodium salt by dissolving in aqueous solution of sodium hydroxide to improve solubility and drug release. Lactose monohydrate and microcrystalline cellulose were used as diluents. Starch paste is prepared in purified water and was used as the binder. Sodium starch glycolate is added as a disintegrating agent. Magnesium stearate was used as the lubricant. The prepared granules were compressed into a double-layer compression machine. The tablets thus formulated with higher proportion of sodium starch glycolate showed satisfactory physical parameters, and it was found to be stable and in vitro release studies are showed that formulation (F-T5H5) was 101.11% and 99.89% respectively. The formulation T5H5 is further selected and compared with the release profile of the innovator product, and was found to be similar (f2 factor) to that of the marketed product. The results suggest the feasibility of developing bilayer tablets consisting of telmisartan and hydrochlorothiazide for the convenience of patients with hypertension.

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