Solubility

Preformulation is a group of studies that focus on the physicochemical properties of a new drug candidate that could affect the drug performance and the development of a dosage form. This could provide important information for formulation design or support the need for molecular modification. Every drug has intrinsic chemical and physical properties which has been consider before development of pharmaceutical formulation. This property provides the framework for drugs combination with pharmaceutical ingredient in the fabrication of dosage form. Objective of Preformulation study is to develop the elegant, stable, effective and safe dosage form by establishing kinetic rate profile, compatibility with the other ingredients and establish physico-chemical parameter of new drug substances. Among these properties drug solubility, partition coefficient, dissolution rate, polymorphic forms and solubility are plays important role in Preformulation study. Polymorphism having crystal and amorphous forms shows different chemical, physical and therapeutic description of the drug molecule. This article explains some properties and therapeutic for Preformulation parameters of drug.

The objective of the present work was to formulate and evaluate novel self-nano emulsifying drug delivery system (SNEDDS) of poorly soluble drug Nateglinide. Poor water solubility and slow dissolution rate are major issues for most upcoming and existing biologically active pharmaceutical compounds. Nateglinide is Biopharmaceutical Classification System Class-II drug that has low solubility and high permeability. Surfactants and oil was selected based on solubility studies were further screened for their efficiency in formulation. Acrosyl K-135 was used as oil phase and Kolliphor RH 40 and Transcutol P were used as surfactant and co-surfactant respectively for formulation. Formulation F13 was found to be optimized formulation on the basis of in vitro dissolution studies, particle size and zeta potential. The particle size of the optimized SNEDDS formulation was found to be 74.6 nm and Z-Average was found to be 43.1 nm, indicating all the particles were in the nanometer range and the zeta potential of the optimized SNEDDS formulation was found to be -18.4 mV. The optimized formulation was then subjected to stability studies and was found to be stable after 6 months. Thus, the study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of Nateglinide to improve its solubility.

Lovastatin belongs to the class of cholesterol lowering drugs and is the first clinically used statin. It is available as conventional and extended release tablets, but its low aqueous solubility finally escorts it to low oral bioavailability (less than 5 %). Therefore, improvement in aqueous solubility of Lovastatin is the foremost aim. In the present work Self-nanoemulsifying drug delivery systems (SNEDDS) of Lovastatin is being formulated to increase the water solubility. Lovastatin SNEDDS was formulated with various oils, surfactants and co-surfactants and tested for its maximum solubility and drug release. The optimized Lovastatin SNEDDS formulation (F8) has a composition of Acrysol EL 135 as oil phase, Lauro glycol 90 and Capmul MCM as surfactant and co-surfactant respectively. Formulation F8 was found to be best formulation based on evaluation parameters. No drug precipitation or phase separation was observed in the optimized formulation. The particle size of the optimized formulation was found to be 4.9 nm & Z-Average of 71.5 nm indicating all the particles were in the nanometer range. The zeta potential of the optimized SNEDDS formulation was found to be -13.7 mV which comply with the requirement of the zeta potential for stability. The current investigation of nano emulsion may serve as a promising approach for the formulation development of poorly soluble drug Lovastatin, which has undoubtedly proved the potential effectiveness of SNEDDS for formulating Lovastatin with improved solubility and dissolution. Key words: Lovastatin, SNEDDS, Statin, Lauro Glycol 90, Solubility  

Naringenin is a flavonoid which has been used for its wide pharmacological action from ancient years including as antidiabetic agent. Naringenin is a lipophilic drug (BCS-II) and have low water solubility (1 in 1000), bioavailability (<25%) and have short half-life (t1/2 =1.3 -2.2h). Nanocrystals is an approach to increase the therapeutic performance of poorly water soluble drugs. The purpose of the present study was to prepare nanocrystalss of naringenin to improve bioavailability and increase therapeutic efficacy. Nanocrystalss of naringenin were prepared by antisolvent precipitation method. The stabilizers used to improve aggregation and increase the solubility. Nanocrystals were characterized for particle size, morphology, release profile and thermal analysis.

The purpose of this research work was to formulate fast dissolving film of cefpodoxime proxetil for oral delivery in order to improve oral bioavailability of drug with poor solubility. Cefpodoxime proxetil (CP) is the drug candidate belonging to BCS class IV with poor solubility and poor permeability is and limited oral bioavailability, an orally administered, extended spectrum, semi-synthetic β- lactum antibiotic of cephalosporin class. To improve oral bioavailability, cefpodoxime proxetil nanosuspension was prepared using solvent-antisolvent precipitation technique. Nanosuspension was characterized on the basis of drug concentration in organic phase, temperature, solvent-antisolvent ratio and the time period of stirring on the particle size systematically. Particle size and zeta potential of nanosuspension was observed at 755.6nm and −22.6mV, respectively. Solvent casting method be used in the formation of film, utilizing HPMC E50 as film former, PEG 400 as plasticizer and tween 80 as surfactant. The optimized fast dissolving film formulation F1 showed uniformity of weight (0.091mg), folding endurance (149) drug content uniformity (99.5%), surface pH (6.8) disintegration time (32 seconds in 6.8 PB) and in- vitro drug release 94.2% in 7 min. So, it is concluded from comparison studies between fast dissolving film (FDF) containing pure drug and nanosuspension, fast dissolving film containing cefpodoxime proxetil nanosuspension gives faster and high drug release.

Aim of present study was to develop self emulsifying drug delivery system (SEDDS) for enhancement of solubility, dissolution rate and oral bioavailability of model drug Rilpivirine. Fifteen formulations were prepared using different oils, surfactants and co-surfactants. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. Further, the resultant formulations were investigated for clarity, phase separation, drug content, % transmittance, globule size, freeze-thaw stability and in vitro dissolution studies. On the basis of dissolution profile and other above mentioned studies, F5 was found to be the best formulation of Rilpivirine SEDDS which contains Captex 355(Oil), Kolliphor RH 40 (Surfactant) and PG (Co-surfactant). In vivo studies revealed that the oral bioavailability of Rilpivirine from SEDDS was 2.2-fold higher compared to that of pure Rilpivirine suspension in rats, suggesting a significant increase (p

Poor aqueous solubility of drugs is a major limiting factor with many new drugs in their successful launch in market in spite of their potential pharmacokinetic activity. Poorly water soluble drugs are becoming a problem in terms of obtaining satisfactory dissolution within the gastro intestinal tract, which is necessary for good bioavailability. Poorly water-soluble drugs are associated with slow drug dissolution followed by slow absorption leading eventually to inadequate and variable bioavailability. Various approaches to overcome the poor aqueous solubility of drugs have been investigated like solid dispersion, spherical agglomeration, nanoparticles, nanosuspensions, nanomorphs, nanocrystals, micronization, polymorphism, co-solvency, pH adjustment, use of surfactants, microemulsion, complexation. In this article, the basic approaches for enhancement of solubility and dissolution of poorly water-soluble drugs have been reviewed with literature-based examples of the formulation options for poorly water-soluble compounds and their practical applications to the industrial practices.

Drugs belonging to BCS class II, low solubility and high permeability; undergo dissolution-rate limited gastrointestinal absorption. Glimepiride is one of the famous drugs belonging to BCS class II. Its poor aqueous solubility usually causes poor dissolution and unpredicted bioavailability. Hence, formulation techniques that accelerate drug dissolution can guarantee a parallel improvement in bioavailability. Now a days different techniques are available to enhance the solubility of drug like co-solvent, solid dispersion, chemical modification of drug, liquisolid technique etc. One of the favorable strategy to improve the solubility and hence bioavailability of poorly water soluble drugs is theformulation of solid dispersion. The solid dispersion may be prepared by solvent evaporation method, melting method, melt solvent method, kneading method, co-grinding method, co-precipitation method, modified solvent evaporation method, spray drying, gel entrapment techniqueand co-precipitation with supercritical fluid. This review article comprises of the research materialized in the field of solubility and dissolution enhancement of glimepiride.

Cefixime has bioavailability of 40-50%, which could be attributed to its low solubility in GI tract. The objective of this pilot study was to compare the efficacy and safety of improved formulation of cefixime 200 mg tablet (CEFOLAC) versus conventional marketed cefixime 200 mg tablet in patients with typhoid fever (TF). Patients with clinical diagnosis of TF were randomized to receive either treatment twice daily for 10 days. Primary efficacy end point was reduction of clinical symptoms score on day 5 and number of patients with absence of clinical symptoms. Secondary endpoints include microbiological cure and clinical relapse on day 10 and 21. Total 22 patients completed study successfully and were subjected to analysis. Percentage improvement in total clinical symptoms score from baseline to day 5 was greater in improved formulation of cefixime (70 %) than conventional cefixime 200 mg tablet (58 %). On day 5, numbers of patients with complete cure of clinical symptoms were greater in group A as compared to group B. All patients in both the groups were cured based on clinical symptoms and microbiological evaluation on day 10 and day 21. No case of clinical relapse was observed. Both the formulations of cefixime were well tolerated by patients. Improved formulation of cefixime offers faster and greater improvement in clinical symptoms than conventional cefixime tablet in patients with TF. Improved formulation of cefixime is a better option for the treatment of patients with TF than conventional cefixime tablet.

Enhancement of the solubility, dissolution and bioavailability of the drugs is the challenging task for the research sector. As many of the solubility enhancement techniques are available to achieve the desired goal, but the older techniques don’t show the expected results for solubility enhancement and bioavailability as well, and they are unstable also some time.  But today the scenario is different because the novel techniques of solubility enhancement are available, such as hydrotropy, supercritical fluid process, sonocrystallisation, inclusion complex system, spray drying, microwave assisted techniques, etc. this novel techniques have the ability to give the reproducible results for solubility enhancement in pharmaceutical product development.  present review article deals with the different techniques for the solubility enhancement of the poorly soluble drug candidates.