Designing Paclitaxel drug delivery systems aimed at improved patient outcomes: current status and challenges.

Paclitaxel is one of the most widely used and effective antineoplastic agents derived from natural sources. It has a wide spectrum of antitumor activity, particularly against ovarian cancer, breast cancer, nonsmall cell lung cancer, head and neck tumors, Kaposi's sarcoma, and urologic malignancies. It is a highly lipophilic compound with a log P value of 3.96 and very poor aqueous solubility of less than 0.01 mg/mL. In addition, the compound lacks functional groups that are ionizable which could potentially lead to an increase in its solubility with the alteration in pH. Therefore, the delivery of paclitaxel is associated with substantial challenges. Until the introduction of Abraxane, only commercial formulation was solution of paclitaxel in cremophor, which caused severe side effects. However, in recent years, a number of approaches have been reported to solubilize paclitaxel using cosolvents and inclusion complexes. In addition, innovative approaches have been reported for passive targeting of tumors using nanoparticles, nanosuspensions, liposomes, emulsions, micelles, implants, pastes and gels. All approaches for delivery of improved therapeutic outcome have been discussed in this paper.

Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation.

The purpose of this study was to evaluate mannitol as filler along with microcrystalline cellulose (MCC) in wet granulated tablet formulation, in situations where lactose cannot be included in the formulation due to chemical incompatibility with the active drug. A two-level full factorial design with two center points was used to study the effect of three variables: mannitol: MCC ratio (mannitol weight fraction of the filler; low 0 (no mannitol) and high 0.5), water to intragranular solids ratio (low 0.25 and high 0.4) and magnesium stearate concentration, w/w (0.6% low and 1.2% high). The response variables evaluated were granulation compactibility, ejection force, normalized granule size, % fines, flowability index, compression speed sensitivity and hardness loss upon storage. Addition of mannitol in the MCC formulation increased compactibility of the final granulation as it decreased the susceptibility of the formulation to compaction loss upon wet granulation. Presence of mannitol in the formulation reduced the compression speed sensitivity and also decreased the susceptibility of the formulation to hardness loss upon storage.

Effect of excipient and processing variables on adhesive properties and release profile of pentoxifylline from mucoadhesive tablets.

The bioavailability and onset of action of drugs with high first-pass metabolism can be significantly improved by administration via the sublingual route. The objective of this study was to evaluate the effect of polymer type and tablet compaction parameters on the adhesive properties and drug release profile from mucoadhesive sublingual tablet formulations. Pentoxifylline was selected as the model drug because it has poor oral bioavailability due to extensive first-pass metabolism. Two polymers known to possess mucoadhesive properties, carbomer and hydroxypropyl methyl cellulose (HPMC), were used to prepare the formulations. Tablets were prepared by using direct compression technique and evaluated for in vitro dissolution, drug-excipient interactions, and adhesive properties. In general, there was a decrease in the rate of drug release with an increase in the concentration of polymers. No drug-excipient interactions were evident from differential scanning calorimetry or high-performance liquid chromatography analysis. For the formulations containing HPMC, the force of mucoadhesion increased with an increase in the concentration of polymer; however, for carbomer formulations, no such correlation was observed. Force of mucoadhesion decreased as a function of hydration time in both of the polymers.