The Effect of Process Parameters on the Microstructure, Stability, and Sensorial Properties of an Emulsion Cream Formulation.

A classical emulsion formulation based on petrolatum and mineral oil as the internal phase with emulsifier wax as a typical topical emulsion cream was investigated for the effect of process parameters on drug product quality and performance attributes. The Initial Design of Experiment (DoE) suggested that an oil phase above 15%, coupled with less than 10% emulsifying wax, resulted in less stable emulsions. Different processing parameters such as homogenization speed, duration, cooling rate, and final temperature showed minimal influence on properties and failed to improve stability.

Influence of Manufacturing Process on the Microstructure, Stability, and Sensorial Properties of a Topical Ointment Formulation.

The manufacturing process for ointments typically involves a series of heating, cooling, and mixing steps. Precise control of the level of mixing through homogenization and the cooling rate, as well as temperature at different stages, is important in delivering ointments with the desired quality attributes, stability, and performance. In this work, we investigated the influence of typical plant processing conditions on the microstructure, stability, and sensorial properties of a model ointment system through a Design of Experiments (DoE) approach.

Assessing and Predicting Physical Stability of Emulsion-Based Topical Semisolid Products: A Review.

The emulsion-based topical semisolid dosage forms present a high degree of complexity due to their microstructures which is apparent from their compositions comprising at least two immiscible liquid phases, often times of high viscosity. These complex microstructures are thermodynamically unstable, and the physical stability of such preparations is governed by formulation parameters such as phase volume ratio, type of emulsifiers and their concentration, HLB value of the emulsifier, as well as by process parameters such as homogenizer speed, time, temperature etc. Therefore, a detailed understanding of the microstructure in the DP and critical factors that influence the stability of emulsions is essential to ensure the quality and shelf-life of emulsion-based topical semisolid products.

Crystallization and Rheology of Mono- and Diglycerides and Their Role in Stabilization of Emulsion Droplets in Model Topical Ointments.

The crystallization behavior of commercial mono- and diglycerides (MDG) in paraffin oil is studied to develop an in-depth understanding of the polymorphic transitions useful for the physical stability of petroleum oil-based topical emulsions. Optical microscopy and differential scanning calorimetry measurements showed the formation of plate-like and spherulite crystals at high and low temperatures, in sequence, while cooling a solution of MDG dissolved in oil. High-resolution NMR and X-ray scattering demonstrate that 1-monoglycerides (mixture of 1-glyceride monostearate and 1-glyceride monopalmitate) cocrystallize to an inverse-lamellar structure (L polymorph) that mainly forms plate-like crystals at a higher temperature.

API-polymer interactions in Sepineo P600 based topical gel formulation- impact on rheology.

In the present study, topical gel and emulsion gel were formulated using Acrylamide/ Sodium Acryloyldimethyl taurate copolymer (Sepineo P600) as a gelling agent, and their rheological attributes and physical stability were evaluated upon incorporation of API. Lidocaine, a free base drug (pK 7.92) was used as a model drug in all formulations.

Model for Long Acting Injectables (Depot Formulation) Based on Pharmacokinetics and Physical Chemical Properties.

The objective was to develop a model to a priori identify the most suitable depot technology for a candidate based upon its therapeutic index (TI), pharmacokinetics (PK), and physical chemical properties. A depot map of release rates needed to achieve target PK in TI against release rates predicted based on intrinsic dissolution rate (IDR) and particle size (PS) clearly identified three zones: (a) products and candidates around the line of identity for which suspension is the appropriate depot technology, (b) area to the right of line of identity in which depot candidates would require a controlled release technology such as PLGA microspheres since in vivo release rate needed for PK in TI is significantly lower than predicted based on IDR and PS, and (c) area to the left of the line of identity where IDR is not sufficient to achieve target in vivo release rate for PK in TI and hence enhanced dissolution is needed such as with nanoparticles. Dose-solubility technology map of approved depot products and candidates showed clusters of products around a depot technology such as suspensions and microspheres, for drugs with high dose/low solubility and low dose/high solubility compounds, respectively.

Delineating the role of cooperativity in the design of potent PROTACs for BTK.

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that simultaneously bind to a target protein and an E3 ligase, thereby leading to ubiquitination and subsequent degradation of the target. They present an exciting opportunity to modulate proteins in a manner independent of enzymatic or signaling activity. As such, they have recently emerged as an attractive mechanism to explore previously "undruggable" targets.

In vitro and in vivo characterization of amorphous, nanocrystalline, and crystalline ziprasidone formulations.

Ziprasidone, commercially available as Geodon capsules, is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorder. It is a BCS Class II drug that shows up to a 2-fold increase in absorption in the presence of food. Because compliance is a major issue in this patient population, we developed and characterized solubilized formulations of ziprasidone in an effort to improve absorption in the fasted state, thereby resulting in a reduced food effect.

Effect of cyclodextrin derivation and amorphous state of complex on accelerated degradation of ziprasidone.

Inclusion complexes of ziprasidone with several β-cyclodextrins [β-CDs; sulfobutylether-β-cyclodextrins (SBEβCD), hydroxypropyl-β-cyclodextrins (HPβCD), methyl-β-cyclodextrins (MβCD), and carboxyethyl-β-cyclodextrins (CEβCD)] were prepared and solution stability was evaluated at elevated temperature. Solid-state stability was assessed by subjecting various CD complexes of ziprasidone, spray-dried dispersion (SDD), partially crystalline ziprasidone-SBEβCD salts, and the physical mixture of ziprasidone-SBEβCD to γ-irradiation. Degradant I was formed by oxidation of ziprasidone, which upon aldol condensation with ziprasidone formed degradant II in both solution and solid states.

Influence of dosage form on the intravitreal pharmacokinetics of diclofenac.

Purpose: To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits.

Methods: Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.

Prediction of vitreal half-life based on drug physicochemical properties: quantitative structure-pharmacokinetic relationships (QSPKR).

Purpose: The aim of this study was to develop quantitative structure pharmacokinetic relationships (QSPKR) to correlate drug physicochemical properties (molecular weight, lipophilicity, and drug solubility), dose, salt form factor, and eye pigmentation factor to intravitreal half-life in the rabbit model.

Methods: Dataset derived from prior literature reports, which included molecules with complete structural diversity, was used to develop the QSPKR models. Entire dataset as well as subsets limited to albino rabbit data, pigmented rabbit data, acids, bases, zwitterions, neutral compounds, suspensions, and macromolecules were analyzed.

Local delivery of vancomycin for the prophylaxis of prosthetic device-related infections.

Purpose: To evaluate the in vivo efficacy and pharmacokinetics of vancomycin delivered from glycerylmonostearate (GMS) implants in a prosthetic-device based biofilm infection model.

Methods: A biofilm infection model was developed in male Sprague-Dawley rats by implanting a vascular graft on the dorsal side of each rat and infecting it with 1.5 x 10(8) cfu/ml Staphylococcus epidermidis.

Hydrolysis in pharmaceutical formulations.

This literature review presents hydrolysis of active pharmaceutical ingredients as well as the effects on dosage form stability due to hydrolysis of excipients. Mechanisms and measurement methods are discussed and recommendations for formulation stabilization are listed.