PELLETS AND PELLETIZATION: EMERGING TRENDS IN THE PHARMA INDUSTRY.

The present time is considered as an era of advancements in drug delivery systems. Different novel approaches are under investigation that range from uniparticulate to multi particulate system, macro to micro and nano particulate systems. Pelletization is one of the novel drug delivery technique that provides an effective way to deliver the drug in modified pattern. It is advantageous in providing site specific delivery of the drug. Drugs with unpleasant taste, poor bioavailability and short biological half-life can be delivered efficiently through pellets. Their reduced size makes them more valuable as compared to the conventional drug deliv- ery system. Different techniques are used to fabricate the pellets such as extrusion and spheronization, hot melt extrusion, powder layering, suspension or solution layering, freeze pelletization and pelletization by direct compression method. Various natural polymers including xanthan gum, guar gum, tragacanth and gum acacia, semisynthetic polymers like cellulose derivatives, synthetic polymers like derivatives of acrylamides, can be used in pellets formulation. Information provided in this review is collected from various national and intemational research articles, review articles and literature available in the books. The purpose of the current review is to discuss pellets, their characterizations, different techniques of pelletization and the polymers with potential of being suitable for pellets formulation.

Preparation and Characterization of Solid Dispersions of Artemether by Freeze-Dried Method.

Solid dispersions of artemether and polyethylene glycol 6000 (PEG6000) were prepared in ratio 12 : 88 (group-1). Self-emulsified solid dispersions of artemether were prepared by using polyethylene glycol 6000, Cremophor-A25, olive oil, Transcutol, and hydroxypropyl methylcellulose (HPMC) in ratio 12 : 75 : 5 : 4 : 2 : 2, respectively (group-2). In third group, only Cremophor-A25 was replaced with Poloxamer 188 compared to group-2. The solid dispersions and self-emulsified solid dispersions were prepared by physical and freeze dried methods, respectively. All samples were characterized by X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimeter, scanning electron microscopy, and solubility, dissolution, and stability studies. X-ray diffraction pattern revealed artemether complete crystalline, whereas physical mixture and freeze-dried mixture of all three groups showed reduced peak intensities. In attenuated total reflectance Fourier transform infrared spectroscopy spectra, C-H stretching vibrations of artemether were masked in all prepared samples, while C-H stretching vibrations were representative of polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188. Differential scanning calorimetry showed decreased melting endotherm and increased enthalpy change (ΔH) in both physical mixture and freeze-dried mixtures of all groups. Scanning electron microscopy of freeze-dried mixtures of all samples showed glassy appearance, size reduction, and embedment, while their physical mixture showed size reduction and embedment of artemether by excipients. In group-1, solubility was improved up to 15 times, whereas group-2 showed up to 121 times increase but, in group-3, when Poloxamer 188 was used instead of Cremophor-A25, solubility of freeze-dried mixtures was increased up to 135 times. In fasted state simulated gastric fluid at pH 1.6, the dissolution of physical mixture was increased up to 12 times and freeze-dried mixtures up to 15 times. The stability of artemether was substantially enhanced in freeze-dried mixtures by using polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188 of self-emulsified solid dispersions of artemether in Hank's balanced salt solution at pH 7.4.

Improved physicochemical characteristics of artemisinin using succinic acid.

Artemisinin (ARMN) is a potent antimalarial drug, which is effective against multidrug resistant strains of Plasmodium falciparum and produces rapid recovery even in patients with cerebral malaria. Being poorly soluble in water, artemisinin is incompletely absorbed after oral intake due to poor dissolution characteristics in the intestinal fluids. To enhance these properties, solid dispersions of artemisinin with succinic acid (SUC) were prepared using drug-carrier ratios 1 : 1, 1 : 4, 1 : 6, 1 : 8 and 1 : 10 by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), x-ray diffraction patterns (XRD), phase solubility and dissolution kinetics evaluated by applying zero order, first order, Higuchi, and Korsmeyer-Peppas models. Physical mixtures produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. The dissolution profiles of all formulations followed Higuchi model and exhibited diffusion-controlled release of drug. Solvent evaporation method (SLVPs) exhibited improved solubility and freeze dried solid dispersions (FDSDs) produced highest solubility but stability constant was opposite. ARMN and SUC both were found completely crystalline as shown by their XRD patterns. Physical mixtures (PMs) showed reduced intensity in their XRD patterns while solid dispersions by SLVPs exhibited twice reduced intensity and much displaced angles, whereas FDSDs showed synergistic effects in some of ARMN and SUC peaks. DSC thermograms of FDSDs at drug-carrier ratios 1 : 1-1 : 4 showed lower melting temperature and enthalpy change (deltaH) values than respective SLVPs, whereas at higher ratios, a reverse was true. SLVPs showed displaced methyl stretching bands at lower drug-carrier ratios and exhibited O-H stretching characteristic bands of SUC at higher drug-carrier ratios. In addition, carbonyl group and C-O stretching vibrations characteristic of SUC (1307 cm(-1)) appeared prominently compared to PMs, whereas C-O stretching characteristic bands of ARMN disappeared at higher ratios. FDSDs exhibited distinct nature of bonding compared to respective SLVPs and PMs.

Malaria and artemisinin derivatives: an updated review.

Malaria is the world's most prevalent disease that affects 515-600 million people each year and about 40% of the world's population live at risk for this infection. The prevalence of morbidity and mortality from drug resistant malaria (Plasmodium falciparum) is increasing in most of the developing countries, which is also a global threat because international travel is common now and imported malaria is increasingly a serious problem. Since rapid schizonticidal action of naturally occurring endoperoxides pharmacophore present in artemisinin against drug-resistant malaria has been documented, researchers have focused more on artemisinin analogs than any other antimalarials. In this review, drugs of choice about malaria i.e. artemisinin and its analogus/derivatives (arteether, artemether, artemiside, artemisinin, artemisone, artesunate, dihydroartemisinin) have been discussed in detail e.g. bioavailability, formulation development, stability, combination therapy, additional benefits, drug resistance and toxicity have been reviewed.

Counter irritant activity of Carthamus oxycantha.

Many locally occurring species of Asteraceae are used as medicinal plants by various tribal and ethnic communities in Pakistan. Carthamus oxycantha is often occurs as weed in cultivated fields. Folk medicines indicated its use as an anti inflammatory and wound healing plant. It is used for wound healing by the local population in the form of powder paste. No scientific Report, about the behavior of this plant has so far been published. The counter irritant studies of locally occurring Carthamus oxycantha was carried out. The main objectives of the project were to evaluate its wound healing effects on animal skin and the identity and characterization of chromatographically isolated fractions. For this purpose, different solvents with a broad range of polarity were successively used to extract non-polar compounds (petroleum ether extract), constituents intermediate polarities (chloroform extract) and polar constituents (methanol extract) from the whole herb of Carthamus oxycantha. The counter irritant activity of the crude extracts and isolated fractions was evaluated on rabbit's skin. Five fractions Co-1 to Co-5 were isolated from the active chloroform extract by column and thin layer chromatography. Co-1, Co-3 and Co-5 appeared to be the most potent counter irritant than others. A possible structure-activity relationship of these active compounds was investigated by using spectroscopy (UV and FTIR analysis).

Isolation and characterization of irritant components of Euphorbia pilulifera L.

Euphorbia pilulifera is commonly found weed along road sides and loamy soils. This weed is commonly used as treatment of female disorders and respiratory problems. The latex of this weed causes irritation on hand on contact. To evaluate its irritant potentials, the dermatological investigation of irritant principles from locally occurring Euphorbia pilulifera was carried out. For this purpose, after collection and drying, a series of solvents with increasing polarity were used for the successive extraction of non-polar compounds (petroleum ether extract), constituents of intermediate polarities (chloroform extract) and polar constituents (methanol extract) from the whole herb of Euphorbia pilulifera. The chloroform extract of this weed was found most irritant to rabbit ' s skin. Chloroform extract was further subjected to column chromatography; four fractions Ep 1 to Ep 4 were isolated from active chloroform extract by column and thin layer chromatography. The irritant potentials of these isolated fractions were evaluated on rabbit 's skin. Two fractions out of the four, Ep 1 and Ep 3 appeared to be the most irritant than others. A possible structure activity relationship of these active compounds was discussed in order to establish their activity.

Hypoglycemic activity of Ficus racemosa bark in combination with oral hypoglycemic drug in diabetic human.

Medicinal herbs, used in indigenous medicines in crude forms for the management of diabetes mellitus, contain both the organic and inorganic constituents. The aim of the study was to find out the hypoglycemic effect of Ficus racemosa in a group of diabetic subjects taking oral hypoglycemic drug. Twenty five of each, male and female, diabetic patients, selected from Fatima Jinnah Medical College, Lahore, Pakistan, taking oral hypoglycemic drug were included in this study and were given orally the extract (5 mL) of bark of Ficus racemosa (about 100 mg) two times for 15 days. Blood samples for estimation of blood glucose and parameters of liver and renal functions were estimated. It was observed that after taking the herb in combination with drug, blood glucose level (fasting and after breakfast) was markedly decreased in both male and female but significant difference was only observed in sugar level of males after 1.5 h after breakfast. To rule out herb toxicity, liver and renal functions tests of patients was also performed which were observed to be in normal range. Present investigation established a pharmacological evidence to support the folklore claim that Ficus racemosa is good anti-diabetic agent.

N-Acetyl-4-(benzene-sulfonamido)benzene-sulfonamide.

In the mol-ecule of the title compound, C(14)H(14)N(2)O(5)S(2), the dihedral angle between the aromatic rings is 77.75 (9)°. The acetamide group is planar [maximum deviation = 0.002 (3) Å] and oriented at dihedral angles of 13.49 (21) and 73.94 (10)° with respect to the aromatic rings. An intra-molecular C-H⋯O inter-action results in the formation of a six-membered ring. In the crystal structure, inter-molecular N-H⋯O and C-H⋯O inter-actions link the mol-ecules into a three-dimensional network, forming R(2) (2)(20) ring motifs.