pkpd.Release (version 0.1.0)

zero_order_release: Zero-Order Drug Release Kinetic Model

Description

Fits experimental cumulative drug release data to a zero-order kinetic model using linear regression. The function supports optional grouping variables (e.g., formulation, batch) and optional pH-dependent analysis. It can generate publication-quality plots with fitted straight lines and annotations for zero-order rate constant (k0), intercept, coefficient of determination (R^2), and time required for 50-percent drug release (t50).

Value

A list containing:

fitted_parameters

A data frame with k0, intercept, R^2, and t50 values for each group or pH condition.

data

The processed data used for model fitting and plotting.

Arguments

data

A data frame containing experimental drug release data.

time_col

Character string specifying the column name for time (e.g., minutes or hours).

release_col

Character string specifying the column name for cumulative drug release (typically percentage).

group_col

Optional character string specifying a column name used for grouping (e.g., formulation, batch). Default is NULL.

pH_col

Optional character string specifying a column name containing pH values. If provided, zero-order models are fitted separately for each pH.

plot

Logical; if TRUE, generates a plot of experimental data with zero-order fitted straight lines (default is TRUE).

annotate

Logical; if TRUE, annotates the plot with k0, intercept, R^2, and t50 values for each group (default is TRUE).

Author

Paul Angelo C. Manlapaz

References

Higuchi, T. (1961) <doi:10.1002/jps.2600501018> Rate of release of medicaments from ointment bases containing drugs in suspension. Journal of Pharmaceutical Sciences, 50(10), 874–875.

Examples

# Example I: Single formulation
df_1 <- data.frame(
  time = c(0, 15, 30, 45, 60, 90, 120, 150, 180),
  release = c(0, 11.4, 20.8, 30.8, 39.8, 57.8, 72, 84.8, 93.5)
)
zero_order_release(
  data = df_1,
  time_col = "time",
  release_col = "release"
)

# Example II: Two formulations (grouped, not pH-dependent)
df_2 <- data.frame(
  time = rep(c(0, 30, 60, 90, 120, 150), 2),
  release = c(
    0, 18, 35, 55, 72, 88,   # Formulation A
    0, 12, 26, 40, 58, 70    # Formulation B
  ),
  formulation = rep(c("Formulation A", "Formulation B"), each = 6)
)
zero_order_release(
  data = df_2,
  time_col = "time",
  release_col = "release",
  group_col = "formulation"
)

# Example III: pH-dependent release
df_pH <- data.frame(
  time = rep(c(0, 60, 120, 180), 2),
  release = c(0, 40, 75, 95, 0, 30, 60, 80),
  pH = rep(c(7.4, 4.5), each = 4)
)
zero_order_release(
  data = df_pH,
  time_col = "time",
  release_col = "release",
  pH_col = "pH"
)

# Example IV: Two formulations under two pH conditions
df1 <- data.frame(
  time = rep(c(0, 30, 60, 90, 120, 150, 180), 2),
  release = c(
    0, 12, 25, 38, 52, 65, 78,   # pH 4.5
    0, 15, 30, 47, 63, 78, 90    # pH 7.6
  ),
  pH = rep(c(4.5, 7.6), each = 7)
)
df2 <- data.frame(
  time = rep(c(0, 20, 40, 60, 80, 100, 120), 2),
  release = c(
    0, 10, 22, 35, 50, 64, 77,   # pH 4.5
    0, 14, 28, 45, 61, 76, 88    # pH 7.6
  ),
  pH = rep(c(4.5, 7.6), each = 7)
)
df_all <- rbind(
  cbind(dataset = "Dataset 1", df1),
  cbind(dataset = "Dataset 2", df2)
)
zero_order_release(
  data = df_all,
  time_col = "time",
  release_col = "release",
  group_col = "dataset",
  pH_col = "pH"
)